AK's Rambling Thoughts

The Azolla Alternative

2011-10-25T16:36:00.003-05:00

The recent pre-publication of four papers by the Berkeley Earth Surface Temperature team has raised the level of furor in at least some venues over the future (if any) of the IPCC and how to handle the issues of rising CO₂. I've discussed this in another venue, along with my confidence in remediation (CO₂ draw-down) as preferable to expensive efforts at mitigation.

I'm going to put a few numbers behind this statement:

With the right approach, IMO, we could start a process today that would probably result in the ability to draw down CO₂ within a 5-10 year active time, using (bio-)technology that might mature within 20 years.

Now, let's start with assuming a 100ppm (parts per million) draw-down, which would be equivalent to reducing our current level of ~400ppm to 300ppm, equivalent to a date prior to 1960. Just how much carbon would we have to remove from the atmosphere?

The density of the atmosphere at sea level is about 1Kg/M³, and the pressure is roughly 10 tons/M². Now, the average molecular weight of air is about 29, while the average molecular weight of CO₂ is about 44. Parts per million are calculated by volume, which corresponds to number of molecules.

So 100ppm CO₂ would weigh (44/29)*(100/1,000,000)*10,000Kg/M² = ~1.5Kg/M². The carbon would be about 12/44 of that, or about 414g/M², or 414 tons/Km². The Earth's surface area is about 5.1*10⁸Km², which adds up to 211.17GTon carbon to be removed. Given the nuclear connotations of "gigaton", I'm going to call it Petagrams (Pg), which is common in carbon literature.

The Azolla Event

About 50 million years ago (MYA), there occurred an event of global importance called the Eocene Azolla event. Evidence suggests it began around 49.3MYA, lasting until around 48.1MYA, thus lasting about 1.2MY.^[1] In this event, it appears that fresh water from Arctic rivers formed a layer over the surface of the heavier salt water, and the entire Arctic (or large parts of it) experienced a massive bloom of a fern called Azolla.

Azolla is an intriguing plant, actually a symbiosis between a secondarily degenerate fern (Azolla sp.) and a blue green algae (Anabaena azollae). It's just a few inches in size, and floats entirely on water, without normally anchoring. It's one of the fastest growing plants known, capable of producing 25-90gm/day/M².^[2] It normally expands vegetatively, although under appropriate circumstances it will reproduce sexually.^[3]

The speed with with the Eocene Azolla grew appears to have been such that it reduced the atmospheric level of CO₂ from 3500ppm to 650ppm,^[4] probably within that small 1.2 million year stretch.^[5] Thus, it makes a great candidate for drawing down CO₂.

Let's do some more numbers. The circumstances under which Wagner grew Azolla Nilotica were probably not as optimized as could be done with modern technology, and I'm going to assume that harvesting processes could keep the Azolla growing at maximum rate continuously. 90 gm/day/M² is equivalent to the same number of tons/Km²/day, multiplied by 360 gives 32,400 tons of biomass/Km²/year. Carbon content for various European strains of Azolla ranged from 37-42%.^[6] I'm going to assume 40% (by weight) coming to 12,969, or roughly 13Kilotons Carbon/Km²/year.

Technology

Now comes the technology. I'm going to assume for the moment that within a decade or two we have the technology to float a layer of fresh water on top of salt for very large areas. Later I'll go into possible methods, but for the moment let's just assume one million square kilometers, less than 1/7^th the area of Australia. This works out to 13 Pg (=gigatons)/year. Remember above we said that we have ~212Pg to remove in order to draw-down 100ppm? Dividing 212 by 13 gives about 16.3 years. Double this, and we're down to 8.2 years, triple it and we're down to about 5.5 years. And that's still less than half the area of Australia.

I'm not going to go into detail regarding methods. Fresh water is lighter than sea water at the same temperature, which explains how the fresh water managed to stay separate from underlying salt water during the Azolla Event. The difference is only about 2.5%, however, which is pretty small. The lower levels of the Arctic appear to have been anoxic,^[7] in the same way the Black Sea is today.

It's remotely possible that simply floating a layer of fresh water on top of salt water might work, but I'm going to assume not. Given this, the easiest way I see to handle it is with an intermediate layer of some viscoelastic material, with a density intermediate between fresh and sea water. More material intensive, but perhaps cheaper, might be a sort of "air mattress" with a lot of internal tensile stiffening. Another option would be to maintain a layer of pressurized air topped with a stiff but slightly flexible layer, with water above it.

Obviously, all these options would require a good deal of engineering and development. However, consider the difference between 1991 and today. No cell phones (except huge experimental clunkers that only worked in a few areas). The Internet was just getting set up, and mostly just existed in educational environments. When we look at the difference just 20 years has made, there's no good reason to suppose we couldn't do this.

The total amount of the world's good quality agricultural land is around 16.5 million Km².^[8] I've discussed using 3 million Km². The total amount of lower quality agricultural land in the world is around 43.7 million Km². This has been described in the following terms:

If there is a choice, these soils must not be used for grain crop production, particularly soils belonging to Class IV. All three Classes require important inputs of conservation management. In fact, no grain crop production must be contemplated in the absence of a good conservation plan. Lack of plant nutrients is a major constraint and so a good fertilizer use plan must be adopted. Soil degradation must be continuously monitored. Productivity is not high and so low input farmers must receive considerable support to manage these soils or be discouraged from using them. Land can be set aside for national parks or as biodiversity zones. In the semi-arid areas, they can be managed for range. Risk for sustainable grain crop production is 40-60%.^[9]

As our population expands, methods to manage, control, and maintain these lands will become increasingly expensive, relative to more basic types of agriculture. At the same time, technology to manage activities on the water will be coming down in cost. Very likely, they'll meet at some point, at which point it will be cheaper to build new prime agricultural land floating on the ocean than continue using poorly suited terrestrial land. Long before this happens, simple technologies like that necessary for the Azolla Alternative will have become cost effective.

I'm going to leave economic and political issues for another post.

Refs:

Bocchi, S., Malgioglio, A. (2010) Azolla-Anabaena as a Biofertilizer for Rice Paddy Fields in the Po Valley, a Temperate Rice Area in Northern Italy International Journal of Agronomy Volume 2010 (2010), Article ID 152158, 5 pages doi:10.1155/2010/152158

Eswaran, H., Beinroth, F., Reich, P. (1999) Global Land Resources & Population Supporting Capacity Published in: Eswaran, H., F. Beinroth, and P. Reich. 1999. Global land resources and population supporting capacity. Am. J. Alternative Agric. 14:129-136.

Pearson, P.N., Palmer, M.R. (2000) Atmospheric carbon dioxide concentrations over the past 60 million years Nature 406 (6797): 695–699. doi:10.1038/35021000. PMID 10963587

Speelman, E., Damsté, J.S., März, C., Brumsack, H., Reichart, G. (2010) Arctic Ocean circulation during the anoxic Eocene Azolla event Geophysical Research Abstracts Vol. 12, EGU2010-13875, 2010

Speelman, E.N., Van Kempen, M.M., Barke, J., Brinkhuis, H., Reichart, G.J., Smolders, A.J., Roelofs, J.G., Sangiorgi, F., de Leeuw, J.W., Lotter, A.F., Sinninghe Damsté, J.S. (2009) The Eocene Arctic Azolla bloom: environmental conditions, productivity and carbon drawdown Geobiology (2009),
7, 155–170 DOI: 10.1111/j.1472-4669.2009.00195.x

Wagner, G.M. (1997) Azolla: A Review of Its Biology and Utilization The Botanical Review 63(I): 1-26, January-March 1997

Zahran, H.H., Abo–Ellil, A.H., Al Sherif, E.A. (2007) Propagation, taxonomy and ecophysiological characteristics of the Azolla-Anabaena symbiosis in freshwater habitats of Beni-Suef Governorate (Egypt) Egyptian Journal of Biology, 2007, Vol. 9, pp 1-12

Laccognathus embryi

2011-09-13T16:19:00.004-05:00

I have to share this, although I suspect everybody already has read about it, or soon will. Here's the headline and lead paragraph I read (From Google News):

375M-Year-Old Predatory Fish Prowled North America Before Backboned Animals

A new species of large predatory beast of a fish, packing a powerful bite, was already on the prowl in ancient North American waterways before backboned animals existed, researchers say.

After some searching, I found this:

Predatory Fish Once Prowled Ancient Canadian Arctic

A species of fish previously thought to have only existed in Eastern Europe once prowled ancient North American waterways during the Devonian Period, before backboned animals existed on land. [my emphasis]

I just can't think of a comment fit to publish even on a blog. *Sigh!*

3 Chimpanzee Movies

2011-08-30T16:45:00.011-05:00

From a couple of articles by Kimberley J. Hockings, et als.: Chimpanzees Share Forbidden Fruit, and Road crossing in chimpanzees: A risky business.

Crossing a Road (movie): Note how the first male out stands watch. AFAIK the 2nd and 3rd are young males: apprentices.

Crop Raiding (movie)

Sharing raided food (movie)

I don't have time to discuss the subject at the moment, but I'm guessing these will be interesting. Compare this "hunter’s anecdotal report" quoted from Guillot, 1956, in Dr. Hockings doctoral thesis Human-chimpanzee coexistence at Bossou, the Republic of Guinea: a chimpanzee perspective:

"I remember one strange encounter I had in the jungle. A troop of chimpanzees was crossing the jungle path ahead of me, an old male, the leader, stood glaring at us from a distance of a few paces. At intervals he intensified his gruntings to hurry up the rest of the troop, cursing the stragglers. The last chimpanzee to cross was a terrified female. Suddenly the big male gave a bound towards her, seized her and shook her and grunted at her something we could not interpret. Whatever it was, it forced her to turn back into the bush. She reappeared a moment later, and now, clinging to her back with both hands and feet, was a grimacing little baby chimpanzee, which in her terror she had abandoned. Then she leaped into the air with her baby in her arms and disappeared among the foliage of the trees. All was now in order, and the old male gave a couple of triumphant grunts, made a gesture as much to say that the path was free for me, and disappeared into the jungle, the last of his troop.”

She calls it "largely anthropomorphic and likely to be somewhat embellished, but serves to highlight the protective nature of the adult male chimpanzee during this high-risk encounter." I wonder how embellished it actually was.

Neurology and the Soul

2011-06-07T13:02:00.017-05:00

I've just found time to read John Wilkin's Is the soul something we should be agnostic about?, as well as two posts he links to: Sean M. Carroll's Physics and the Immortality of the Soul and PZ Myers' Ain't no heaven, ain't no afterlife of any kind, either, say the physicists.

Are you folks kidding me? Or has physics actually discovered and verified an underlying source of determinism while my back was turned? Or is everybody missing at least one part of the big picture? (Or am I imagining things?)

The underlying assumption in all these arguments is that there's no way for something going on in "spirit space" to interact with the real world. Now, I don't claim to be the physicist Sean M. Carroll is, in fact my understanding is amateur and older than decoherence. But my understanding is that, in practical terms, quantum indeterminacy still reigns, at least with regard to even theoretically predicting the outcome of local wave function collapse (or, if you wish, "decoherence").

Consider the situation where an action potential arrives at a synapse, and releases a certain amount of neurotransmitter. The number of molecules of neurotransmitter vary within a small range due "indeterminacy", and the number of receptors for that neurotransmitter that are actually active will also vary, depending on many factors within the cell, many of them also slightly "indeterminate". Thus the actual size and shape of the current resulting from that action potential can vary within small limits. (In fact, even with a fixed number of molecules of neurotransmitter and receptors, there will be some variation in current due to indeterminacy of position of each neurotransmitter molecule while diffusing across the synaptic gap.)

Now, let's suppose that that one action potential is just on the border of causing the receiving neuron to fire an action potential. That is, given the current (heh) condition of the nearby dendritic arbor, the amount of current necessary to cause an action potential to fire is right in the middle of the potential variation (in current) due to indeterminacy.

Does the neuron actually fire? Or does it end up in a state of superposed states of firing and not firing? Well, I think we can state that it fires, that is that decoherence has taken place. Do we actually know the source of all the information involved in the decoherence?

We don't, of course. People who state that decoherence has proven that everything happening on the quantum state is completely deterministic are simply projecting their own prejudice (i.e. religious convictions) on what is still a highly controversial field. There's plenty of room in those little wave function collapses for huge amounts of information to flow into our universe.

We certainly don't know how many of the neurons in our brains actually balance on the head of this pin. For that matter, the calculations that go on in the dendrites to integrate the information from the current flows in the synapses also depend on distributed molecules of receptors, most of which open and close "randomly" depending on quantum processes that contain "indeterminacy".

So, is it possible for:

some sort of blob of spirit energy that takes up residence near our brain, and drives around our body like a soccer mom driving an SUV?

as Sean M. Carroll mocks and PZ Myers quotes? Well, conceivably, if we assume these "spirit" people are using the word "energy" metaphorically. (Which they probably are since they don't understand physics or thermodynamics well enough to use it in a technical sense.)

Of course the blobs of "spirit energy", actually some sort of informational phenomenon, would have to have some way of predicting the outcomes of all their interventions in these decoherences. Perhaps time and information work differently in "spirit space". Perhaps they can "see" the potential outcomes of different combinations of interventions directly, rather than having to compute it with incredibly powerful modeling. In the same way, perhaps, that a man riding a balloon can see the road ahead without having to rely on asking passing strangers about it.

Of course, this is all very interesting, and would make a great "magic system" for a fantasy novel, but is there any evidence, no matter how tenuous, that such a thing might be so?

Actually yes. Compared to other anthropoid species, humans have a third or so higher ratio of glial cells to nerve cells in at least on area of the dorsolateral prefrontal cortex (area 9L):

Based on the nonhuman species mean LS regression, humans displayed a 46% greater density of glial cells per neuron than expected.

[...]

From this prediction, glial density in humans fell within the 95% PIs (observed log glial density = 5.19; predicted = 5.02; upper PI = 5.40, lower PI = 4.63) and represented 32% more glia than expected.^[1]

Perhaps the human brain has evolved, over the last few million years, to be "ridden" by a "blob of spirit energy", and supporting the receipt of information from the blob is what requires the extra glial activity.

Of course, the actual increase isn't all that great, and:

The human frontal cortex displays a higher ratio of glia to neurons than in other anthropoid primates. However, this relative increase in glia conforms to allometric scaling expectations, when taking into consideration the dramatic enlargement of the human brain. We suggest that relatively greater numbers of glia in the human neocortex relate to the energetic costs of maintaining larger dendritic arbors and long-range projecting axons in the context of a large brain.^[1]

So this "evidence" is highly tenuous. But that's very different from saying it would require a new formulation of natural law.

So when PZ Myers says:

The biologists' perspective, which is a little less fundamental, is simply that there is no identifiable 'receiver' localized in the brain (no, not even the pineal gland, as Descartes believed), distributed physiological activity is associated with thought, and injury, disease, and pharmacology can all profoundly influence the mind. Furthermore, the way the brain works involves trans-membrane ion fluxes and synaptic activity — it's all electrochemistry and biochemistry. In addition to that new physics, we'd need a new chemistry to explain how spirit interacts with neurotransmitters or gene expression or protein phosphorylation.

Well, we don't need "new" physics (although we would need to add some stuff to the one we have) and we don't need new chemistry. The receiver is distributed, just like the physiological activity.

Despite what atheists would like to believe, there are still big holes in our scientific understanding of the world; big enough to drive the biggest spirit.

For the moment, I'd recommend agnosticism.

Notes:

1. Chet C. Sherwood, Cheryl D. Stimpson, Mary Ann Raghanti, Derek E. Wildman, Monica Uddin, Lawrence I. Grossman, Morris Goodman, John C. Redmond, Christopher J. Bonar, Joseph M. Erwin, and Patrick R. Hof Evolution of increased glia–neuron ratios in the human frontal cortex PNAS September 12, 2006 vol. 103 no. 37 13606-13611 doi: 10.1073/pnas.0605843103

Evolutionary Theory for Creationists

2011-06-05T20:08:00.003-05:00

I was recently informed by a creationist that "evolution is a lie!" I went to the trouble of thinking through and writing down my response, so I thought I'd share it with my readers. I created it as a .PDF so clean copies can be printed for creationists who "don't get" the internet. If you want to print it, or save it as a .PDF, click on the word "File" under "Google docs" over at the top left, and select "Print(PDF)".

Evolutionary Theory for Creationists

Can you tell it was written by an agnostic?

This document is entirely original with me, except that the "old saying" I heard somewhere: I don't remember where, I don't know who said it first, and it's something of a paraphrase anyway. With this post I'm putting this document in the public domain as a public service: feel free to copy, modify, and use the result as you please, for profit or not. (Of course, if you claim credit, you'll be "guilty" of plagiarism, but not (AFAIK) theft.) Credit would be nice, but I don't insist on it.

AK

Thundersnow

2011-02-02T15:20:00.003-06:00

Yesterday's occurrence of thundersnow in Chicago had me looking for explanations. Wiki gave a lightweight summary, with just enough technical jargon to make it hard for a typical reader. Subsequent searching lead me to a bunch of good peer-reviewed data on the electrification of thunderstorms, but little of use understanding thundersnow.^{[3] [4] [5] [6]}

I finally found a very recent survey by David M. Schultz and R. James Vavrek,^[1] which while somewhat technical, gave me the insight I was looking for.

Summarizing everything: Thundersnow occurs when the conditions for thunderstorm-type convection are present at the same time as for general snow (in large amounts). This includes the presence of humid air above the freezing point while general temperatures, especially at the ground, are below freezing. A high lapse-rate is also necessary, in order to drive the rapid updraft which creates hail and/or graupel. Substantial electrification requires this.^[3]

We don't yet know for sure how this electrification is caused,^{[1] [2] [3] [4] [5] [6]} but the best guess involves collisions between growing graupel/hail particles and small ice particles.^{[1] [7]}

Some Personal Observation:

My difficulty finding explanations is explained: we don't even know precisely what mechanisms lead to lightning even in thunderstorms, much less thundersnow (which has been much, much less studied). I had always assumed (and you know what that does) that electrification resulted from friction of ice particles with dry air, somehow I had never previously noticed the absence of this mechanism from those considered. Since both simulations and direct experimental measurements of this process would have been easy even in the 19th century, we can presumably rule this mechanism out.

None of the articles intended for general consumption (that I read) explicitly mentioned that we don't know the mechanism for electrification, which would have saved me considerable time trying to find it. (Although the descriptions of the theories and research were well worth the reading.) This points up a general defect in science reporting: the fact that the public is being kept pretty much in the dark regarding how much isn't really known for sure in science.

Schultz, D., & Vavrek, R. (2009). An overview of thundersnow Weather, 64 (10), 274-277 DOI: 10.1002/wea.376

Links:

1 An overview of thundersnow

2 A Climatology of Thundersnow Events over the Contiguous United States Open Access

3 Thunderstorm Electrification (Semi) Open Access

4 The 29 June 2000 Supercell Observed during STEPS. Part II: Lightning and Charge Structure Open Access

5 Relationships between Convective Storm Kinematics, Precipitation, and Lightning Open Access

6 The Electrical Structure of Thunderstorms(Semi) Open Access

7 The Ice Crystal–Graupel Collision Charging Mechanism of Thunderstorm Electrification Open Access

The Final (so far) Step in Language Evolution

2010-05-30T19:49:00.005-05:00

A recently published paper^[1] has impelled me to discuss a favorite theory of mine, involving the actual stages in which our species language skills evolved. Or rather, the final stage. The paper itself, Dissociating neural subsystems for grammar by contrasting word order and inflection (by Aaron J. Newmana, Ted Supallab, Peter Hauserc, Elissa L. Newportb, and Daphne Bavelier), reports the investigation of differential brain region usage in interpreting two different types of language: inflected and positional.

In inflected language, a word's relationship to the rest of the sentence is determined (communicated) through case markers such as inflections (I'm including agglutinating languages in this class). For instance, the subject of a sentence or clause is identified by different inflection (such as case endings) from the object of a verb or preposition. By contrast, in a positional language (or construction within a language) this information is communicated by its position in the sentence, clause, or phrase.

What Newmana et al. have shown is that different regions of the brain are activated when a hearer (seer, actually, in this case since they studied American Sign Language) encounters phrases or clauses determined by inflection vs. word order:

To summarize, we exploited a property of American Sign Language, unique among languages thus far studied with neuroimaging, to directly compare the neural systems involved in sentence processing when grammatical information was conveyed through word order as opposed to inflectional morphology. Critically, this comparison was made within subjects, while tightly controlling syntactic complexity and semantic content. Reliance on word order (serial position) cues for resolving grammatical dependencies activated a network of areas related to serial working memory. In contrast, the presence of inflectional morphology increased activation in a broadly distributed bilateral network featuring the inferior frontal gyri, the anterior lateral temporal lobes, and the basal ganglia, which have been implicated in building and analyzing grammatical structure. These dissociations are in accord with models of language organization in the brain that attribute specific grammatical functions to distinct neural subregions, but are most consistent with those models that attribute these mapping specificities to the particular cognitive resources required to process various types of linguistic cues.^[1]

The Proposed Theory

Now my theory is that the final stage in the evolution of our language skills involve these inflected (and agglutinating) constructions. Several facts point to this sequence.... (read the rest in the full post)

The simplest form of language is the pidgin, a "simplified language that develops as a means of communication between two or more groups that do not have a language in common". In its simplest form a pidgin might consist of 2-3 word sentences containing a noun and a verb, with perhaps another noun representing the object of the verb.

A common theory is that many such pidgins develop naturally into creoles, which are usually typified by

a lack of inflectional morphology (other than at most two or three inflectional affixes),
a lack of tone on monosyllabic words, and
a lack of semantically opaque word formation.
(Some exceptions to this standard have been noted.) This process might take as little as one generation, leading to the widely accepted hypothesis that children come with "hard-wired" expectations of certain features in a language, and, in essence, they look for them hard enough to find them in their parents' pidgin even though it wasn't really there.^{[5] [A1]}

What I would suggest is that entirely positional languages of this type represented the previous stage of language evolution, with the development of case marking, agreement, and flexible word order as the final evolutionary step.

For any proposed evolutionary step, a selective value must be identified. In this case, I would propose that, very simply, flexible word order enables substantially improved epic poetry,^{[2] [3]} which in turn enables multi-generational transmission of essential myths, which in their turn can encode selectively valuable historical information.^{[4] [7]}

I'm going to defer discussion of the adaptive value of myths, and even epic, for a moment while we take a look at how languages evolve in the presence of writing. Although the earlier forms of a language or protolanguage can be inferred from a study of its current structure, most of our information regarding linguistic development comes from written records of some sort, which means that the culture involved had some contact with writing.

Now if writing can carry information across long time periods, it can to some extent replace epic poetry and myth, reducing the need for full flexibility of word order. This being the case, we should expect the languages of cultures using writing (or in close contact with other cultures that use writing) to show a trend of replacing fully flexible word order constructions with more word-order dependent constructions. And so it is, especially in that most-studied of language groups, Indo-European ("IE"):

It has long been noticed that there are trends in language change, such that certain types of development occur often and in unrelated languages. For instance, English is one of many languages that have formed future markers from a verb of motion. The development of Indo-European adverbial particles to adpositions, apparently independently in its daughter languages, results from reanalysis of underlying structures and is a very early development of configurational syntax in the language family.^[2]

Thus, we can see a general trend from case-marked (inflected) constructions to systems dependent on word order. In English this process has been carried almost to completion. We must note here that the only languages we know about in this group are those of cultures that had, or were in close contact with somebody else who had, writing. I would predict that any IE languages that remained completely isolated from writing likely retained the fully flexible constructions of the parent language, although until we find them in contact with somebody capable of writing down reasonably large amounts of them we wouldn't know about them, and at that time we would find them already evolving towards more positional constructions.

Since the work of Lord and Parry, it's been recognized (with some debate) that the epic in its original entirely oral form was composed "on the fly" for a specific performance.^[A2] The actual basic story might stay the same, but each performance was a unique, one-time, composition made up of "formulas", "a formula being 'an expression which is regularly used, under the same metrical conditions, to express a particular essential idea'^[3]".

The language of epic was thus not an actual spoken dialect but a conventionalised form that developed in a manner typical of orally transmitted poetry and later became a prestigious literary variety.^[2]

We can see, here, that the complete flexibility of word order was a tremendous help in creating formulas to fit any necessary metrical/rhyme pattern. By the time the Arcado/Cypriot dialect of Proto-Greek was being written down the loss of this flexibility was already under weigh, although the epic traditions in old Ionia (what later came to be called Achaea) may have retained the older form.

The older IE [Indo-European] system used case to indicate spatial relations, and any accompanying P-word [prepositional and preverbal particles] added meaning without taking over the case function; but both Mycenaean and classical Greek increasingly used prepositional phrases with the preposition governing the noun phrase and determining its case, even though (from a diachronic perspective) it had been the case functions which originally determined what cases a preposition would govern. In Homer both systems (independent case and configurational syntax) are still present, and [...] a [...] strictly synchronic view of the data is possible if the variation is viewed as the normal outcome of grammaticalisation processes, which typically generate changes which may coexist with the original constructions. Greek speakers must have been able to recognise and produce both free and syntactically restricted uses of P-words for some time while the reanalysis of the constructions was taking place, just as English speakers can use ‘going to’ in two different syntactic constructions.^[2]

Now, it's important to realize that this shift is exactly the one studied by Newmana et al. It involves the switch from a system that "increased activation in a broadly distributed bilateral network featuring the inferior frontal gyri, the anterior lateral temporal lobes, and the basal ganglia," to one that "activated a network of areas related to serial working memory." (Since word-order is an essential part of prepositional (and postpositional) phrases.)

I would argue that as the presence of writing reduced the dependence on epic for essential long-term cultural memory, languages relaxed into the easier, because older and more thoroughly evolved, positional constructions. This relaxation, added to the fact that pidgins and (most, if not all) creoles tend to be positional, point to it being the older, original mode. Indeed, the fact that a well developed temporally serial working memory would have been essential for complex movement in the arboreal environment means that all the building blocks would have been there for many tens of millions of years; the evolution of language simply had to tie to these pre-existing (and mostly pre-adapted) features.

By contrast, the brain structures and circuits needed for inflected language constructions may well have been brand new, or at least substantially adapted from some pre-existing system for handling complex transformations.

At this point we need to consider what selective advantage the capacity for epic poetry, and the myth it transmitted, offered our evolving ancestors.

The Adaptive Value of Myth

Any modern study of myth, IMO, should start with When They Severed Earth from Sky: How the Human Mind Shapes Myth by Elizabeth Wayland Barber & Paul T. Barber. Quoting from the first chapter:

[I]f people were so smart--just like us--100,000 years ago, why do the myths they passed down often seem so preposterous to us? And not just to us. Even ancients like the Greek poet Pindar, who made his living telling such stories ca. 500 B.C., sometimes felt constrained to a disclaimer: "Don't blame me for this tale!" The narrators present these myths as "histories". Yet how can we seriously believe that Perseus turned people to stone by showing them the snaky-locked head of a monster, or that a man named Herakles (or Hercules) held up the sky for a while, slew a nine-headed water monster, moved rivers around, and carried a three-headed dog up from the land of the dead? Or that a man named Methuselah lived for almost a millennium? That an eagle pecked for years at the liver of a god tied to a mountain, or that mortal men--Beowulf, St. George, Siegfried, and Perseus included--actually fought dragons? And how can one view people like the Greeks or the Egyptians, who each believed simultaneously in three or four sun gods, as having intelligence? Didn't they notice a contradiction there? Why did people in so many cultures spend so much time and attention on these collections of quaint stories that we know of as "myths"?

The problem lies not in differing intelligence but in differing resources for the storage and transmission of data. Quite simply, before writing, myths had to serve as transmission systems for information deemed important; but because we--now that we have writing--have forgotten how nonliterate people stored and transmitted information and why it was done that way, we have lost track of how to decode the information often densely compressed into these stories, and they appear to us as mostly gibberish. And so we often dismiss them as silly or try to reinterpret them with psychobabble. As folklorist Adrienne Mayor points out, classicists in particular "tend to read myth as fictional literature, not as natural history" [Mayor 2000b, 192]--not least because humanists typically don't study sciences like geology, palaeontology, and astronomy, and so don't recognize the data. [my emphasis]

One of the most striking examples they give of long-term preservation of information involves the collapse of Mount Mazama to create Crater Lake in Oregon. To briefly summarize, a major underground spirit fell in love with a local girl and when his demand for marriage was rejected had a temper tantrum (and battle with the great spirit in the sky) that blew the top off the mountain, resulting in the present caldera lake.

Geological analysis confirms that there was once a mountain on that spot, and that it erupted violently, spewing around 50 km³ of magma, ash, and lava-bombs until the emptying of its magma chamber caused the caldera walls to collapse inward, forming a pit some 4000 feet deep that later filled with water ([refs]), just as the myth says. Since the eruption happened almost 7700 years ago ([ref]), this myth must have been carried down for nearly eight millennia.

Our own (typical) assumption, as we read something like the Klamath myth, is that since we do not agree with the Klamath explanation for this fiery occurrence, there is nothing worth looking at scientifically in the story. But one of our problems as modern observers of myth (or even observers of events such as car accidents) is that people tend to present their observations and their assumed explanations all tangled up together. On the other hand, if we strip away the explanations proffered but keep and investigate the observations, we can see that the observations in myths are fairly accurate (as far as they go), and at the very least they alert us to something of geological interest that happened in a particular place. Furthermore, if we take for the moment the Kalamath step of assuming that the Curse of Fire was caused by a wilful being (more of this below), then we can see that the quite logical strategy is to placate that being—with a gift, bribe, or sacrifice—which is exactly what they did in their attempt to prevent or delay future destructive eruptions. That is, the myth unrolls logically from its own premises—it is not haphazard. In fact, there are many myths concerning geological events in the Pacific Northwest ([ref]), where until the nineteenth century the population remained stable, that is unreplaced by cultures that had not witnessed the events and therefore did not know what was referred to.^[7]

Note that these mythic memories don't need to be geological:

An example that can serve to illustrate the historical reality lying behind the mythological narration is provided by the famous combat between Heracles and the Hydra of Lerna. The analysis of this famous story deserves some attention because it can provide useful insight regarding the origin and factual basis of a myth, as well as other mechanisms of myth-making ([ref]).

The slaying of the Hydra has been one of the myths most widely considered, since antiquity, to rest on natural processes. The always regenerating many heads of the Hydra have been interpreted as a symbol of the many water-sources feeding the large swamps near Lerna, and the struggle between Hercules and the monster therefore an image of the draining effort. After finally chopping her main ‘head’, said to be immortal, the hero buried it forever, putting a huge and heavy rock on it. Kirk (1974), following an interpretation first proposed by Palaephatus, maintains instead that this myth more likely records ancient political events. In a manner similar to the killing of the Minotaur in the Palace of Knossos, the killing of the Hydra at Lerna, as well as the related myth about the killing of the Nemean lion (the first two labours of Heracles, the Mycenaean hero), seems to contain memories of ancient political events in addition to references about fertility rites.

Strong connections are known to have existed between Lerna until the Early Bronze Age (Lerna III), and the Cretan civilization. The end of Lerna III was in part evidently due to the invasion of the Indo-European Greeks in c. 2200 BC. These patriarchal Indo-European-speaking invaders, from whom later the Mycenaeans would originate, marked the end of the Early Bronze Age in many areas of the East Mediterranean. According to typical Minoan settlement patterns, the political and religious centre and the ‘head’ of the local community, would have been the Palace of Lerna (‘House of Tiles’). The destruction of the Lernean Palace (2300–2200 BC) is marked by the peculiar singularity, seemingly unique in the whole of Greece, that the Palace was buried by the conquerors under an enormous funerary tumulus ([ref]), considered nevertheless an enigma by archaeologists because it contains no tombs.

This unusual tumulus, deliberately positioned above the ‘head’ of the defeated society, strictly corresponds to the huge mythological rock placed by Heracles above the head of the beast ([ref]). As such, the facts described by tradition largely coincide with what can be observed on the site. Even the position of the buried Palace, corresponds to the location of the head of the Hydra, buried in the myth on the side of the road to Elaeus. The mythological account can therefore be regarded as quasi-historical, recalling an Early Bronze Age phase of the Mycenean conquest of the Greek mainland against the Lernean Minoan related settlement. The seeming truth behind the myth, and the relevance of the tumulus itself, apparently was already forgotten by the end of the Middle Helladic period (c. eighteenth–seventeenth century BC), as indicated by the fact that the tumulus was then reoccupied by the village after being left untouched for nearly 500 years. We can thus consider this date as the moment when the local historical memory transmitted by oral tradition became a new myth as transmitted by Hesiod, Ovid, Apollodorus and other ancient writers, because the politico-religious factual story lying behind the myth had been forgotten.[7]

This long-term cultural memory isn't limited to historic events, either. For example, in the Iliad, the process of sacrifice and sacrificial meal is twice described in almost identical language (1.458-469 and 2.421-432). The entire description of the process may have been a single formula.

While we today may see little value in the long-term retention of sacrificial processes, the same technique could have been used for the hunting of animals that are temporarily unavailable, the killing of "monsters" (rare large predators that are making nuisances of themselves), even the manufacture of weapons and other tools requiring materials temporarily unavailable. Even if the precise process has been distorted in the centuries since its last use, it would have given a creative inventor a major "leg up" in recreating it.

Overall, I think we can regard the long-term cultural memory process of myths as offering a major benefit to the population that possesses it.

Epic as a Carrier of Myth

The final link in the chain is either the easiest or the hardest: epic poetry as the primary and most effective carrier of myth. It's generally accepted that poetical systems such as meter, alliteration, assonance, and rhyme, aid in memorizing both complete poems and the poetic formulas used in longer epics.^[3] There is also evidence that these techniques add to the acceptance of the message by the audience.^[9] The use of the formulas in epic, in turn, eases the "on-the-fly" composition during performance. If the story-teller wants to say "next morning", but instead recites "when rosy-fingered dawn the early one appeared", there's much more time for composing the next portion of the performance. The latter formula would fit metric patterns the former would not. Because it's a formula, it doesn't have to actually be composed on the fly, rather the story-teller pulls it from his (or perhaps her) mental toolbox based on its "fit" within the metrical pattern and recites it "on autopilot" while thinking about the following formulas.

We have, then, the following logical sequence:

Poetic tools (meter, etc.) aid in memorization and audience acceptance,
composing epic "on the fly" requires a large toolbox of "formulas" with tight requirements to fit into metrical (and other) slots,
fully flexible word order allows a much larger collection of "formulas",
the use of inflection allows flexible word order,
therefore the capacity to use and understand inflected constructions provides the most effective transmission of any story (mythic or otherwise).

Of course, this sequence is hardly "proven", and testing it probably involves some serious challenges given the widespread influence of written material on just about everybody.

Nevertheless, it provides a coherent model for the development of inflection and the associated tools of flexible word order as an evolutionary adaptation, allowing us to perhaps glimpse the evolutionary precursor to our modern language skills.

Appendices:

A1 "... widely accepted hypothesis that children come with "hard-wired" expectations of certain features in a language": A brief Google search or perusal of the Wiki articles will find many mentions of opposition to this idea. I'm not going to get into this much, IMO this opposition represents the last-ditch defense of the discredited^[6] "blank slate"^[8] concept of human cognition, and thus falls into the same class with the last-ditch opposition to plate tectonics in the '70's, religious opposition to evolution, and the more specious of attempts to "falsify" the "Greenhouse effect".

(Yes, I know some people will feel their sacred oxen have been gored here, but science is about finding the facts, and IMO twisting the facts to support an outdated Marxist ideology of how human cognition works is just as bad as twisting them to support Biblical literalism.)

A2 "... the epic in its original entirely oral form was composed "on the fly" for a specific performance": I'm referring here to conditions before any contact with writing had taken place. Even writing in another culture in close contact with the one under discussion. Obviously, we can only project what this would have been like, since writing of some sort was necessary to preserve the literature itself, at least until Milman Parry began his studies recording oral performances,^[3] and of course writing was already present in the culture he studied. The introduction of writing not only (potentially) replaces some of the essential purpose (value) of epic and other poetry, it permits the permanent preservation of a specific poetic composition, making it available for rote memorization.

It seems likely to me that the appearance of the written Iliad, as well as any other recorded (in writing) performances contemporaneous with it, would have seriously distorted the entire formulaic tradition, potentially distorting our model of what the original, truly pre-literate, epic tradition was like. Barry Powell has suggested that the Greek alphabet was specifically created to record the work of Homer,^[10] especially the Iliad, and while that may be plausible, I find it more likely that the alphabet was created to record the more typical shorter performances found in the Little Iliad and the other poems of the "Epic Cycle".

These performances would have lasted about 2 hours at full speed; if they were dictated at 1/3 speed an entire dictation session would have required about 6 hours, a good day's work for an aoidos and his scribe. Based on Parry's research, only the more skilled of aoidoi would have been able to do this. Alternatively, the inventor of the Greek alphabet might have developed some sort of shorthand allowing him to write at full performance speed.

In the beginning, I suspect that recitals of these dictated poems would have been much less popular than true oral performance: the most likely scenario is a ship captain or other traveler who carried his written texts with him and performed them in locales where (and when) no true aoidos (or rhapsode) was available. Or perhaps he was carrying stories popular in the eastern Aegean Sea (i.e. Chios) to the Ionian settlements in the West.

Once the Greek alphabet was created, and in use (if perhaps only by one man), it seems entirely plausible that a particularly skilled aoidos ("Homer") undertook to create a special masterpiece good for a 20-hour performance. Thus, the Iliad. If the same aoidos also dictated the Odyssey, it seems likely that it was many years later.

We know even less about the process by which the recording of Mesopotamian and Babylonian mythologies interacted with the presence of writing.

Newman, A., Supalla, T., Hauser, P., Newport, E., & Bavelier, D. (2010). Dissociating neural subsystems for grammar by contrasting word order and inflection Proceedings of the National Academy of Sciences, 107 (16), 7539-7544 DOI: 10.1073/pnas.1003174107

Links:

1. Dissociating neural subsystems for grammar by contrasting word order and inflection

2. Prepositions and preverbs in Hellenistic Greek

3. The Singer of Tales by Albert Lord

4. When They Severed Earth from Sky: How the Human Mind Shapes Myth by Elizabeth Wayland Barber & Paul T. Barber

5. The language instinct: how the mind creates language (page 21) by Steven Pinker

6. The fateful hoaxing of Margaret Mead: a historical analysis of her Samoan Research by Derek Freeman

7. Exploring the nature of myth and its role in science

8. The Blank Slate by Steven Pinker

9. Birds of a feather flock conjointly (?): Rhyme as reason in aphorisms

10. Homer and the origin of the Greek alphabet By Barry B. Powell

Animals Without Oxygen

2010-04-07T12:42:00.002-05:00

The recent discovery of animals that appear to live entirely without oxygen^[1] has confirmed a scenario of convergent evolution in the development of hydrogenosomes, demonstrating with near certainty that mitochondria have evolved into hydrogenosomes multiple times. This was already pretty will demonstrated by the discovery of hydrogenosomes with mitochondrial DNA,^{[4] [6] [7]} as well as the fact that they, and mitosomes (similar organelles that do not produce hydrogen) "all share one or more traits in common with mitochondria (Fig. 2), but no traits common to them all, apart from the double membrane and conserved mechanisms of protein import, have been identified so far."^[7]

These animals are members of the phylum Loricifera, which is (distantly) related to arthropods and other members of the general taxon Ecdysozoa.^[1][5] Members of this phylum tend to have very complex life cycles (for metazoans), with at least some species having a parthogenic larval stage intervening between stages of adult sexual reproductions.^[5]

This is an exciting discovery, both in terms of the potential discoveries in energy biochemistry and what it says regarding the overall evolution of the Eukaryotes.

Efforts to pin down the exact "evolutionary tree" of the early Eukaryotes have, more and more, shown a tangled relationship among various proteins (and their coding genes), implicating a large amount of lateral transfer.^[7] The role of mitochondria has changed during this process. At one time the various amitochondrial Eukaryotes were regarded as (possibly) descended from the ancestral premitochondrial Eukaryote. By now, however, it's pretty clear that most (probably all) of these lineages are descended form mitochondrial Eukaryotes.^[7]

To complicate the picture, a number of (probably distantly related) lineages possess mitochondria that are facultative anaerobes.^[8] Among these lineages are several animals such as parasitic helminths such as Fasciola hepatica and Ascaris suum. It seems plausible that the probable hydrogenosomes of these newly discovered Loricifera are descended from such facultatively anaerobic mitochondria. (Or more precisely, descended from the original mitochondria via such facultatively anaerobic mitochondria.)

It's interesting to speculate regarding the specific metabolic pathways these species use. One possibility is that these organelles, despite looking like hydrogenosomes, are actually using sulfate as an electron donor, producing hydrogen sulfide. Another is that they actually produce hydrogen, which is then used by other organisms for energy, to reduce sulfates to hydrogen sulfide. Certainly the former would provide more energy for a multicellular creature. OTOH it would also have (probably) required a longer evolutionary path to reach. The question I suppose, is whether a simple hydrogen-producing metabolism could have provided enough energy for such a creature. It certainly seems plausible that a sulfate (or sulfite) reducing metabolism could have evolved in a facultative anaerobe, followed by streamlining into an obligate anaerobe.

I'm certainly looking forward to the publication of further research on these animals.

T/H Nick Anthis

Danovaro, R., Dell'Anno, A., Pusceddu, A., Gambi, C., Heiner, I., & Kristensen, R. (2010). The first metazoa living in permanently anoxic conditions BMC Biology, 8 (1) DOI: 10.1186/1741-7007-8-30

1 The first metazoa living in permanently anoxic conditions Open Access (Preliminary PDF)

2 Anaerobic Metazoans: No longer an oxymoron Open Access (Preliminary PDF)

3 Anaerobic animals from an ancient, anoxic ecological niche Open Access (Preliminary PDF)

4 Organelles in Blastocystis that Blur the Distinction between Mitochondria and Hydrogenosomes Open Access

5 An Introduction to Loricifera, Cycliophora, and Micrognathozoa Open Access

6 Degenerate mitochondria Open Access

7 Eukaryotic evolution, changes and challenges

8 Mitochondria as we don’t know them

I'm Back! (Sort of)

2010-01-20T09:30:00.003-06:00

I've been rather quiet lately, with a bunch of projects taking up my time and sending me all over the countryside with little opportunity for the internet, and most of that taken up with a recently completed project, the brag for which you may see at the upper left: I was selected to be a judge for Open Lab 2009, in the neurology division, which was sort of flattering, given that my expertise in the subject is entirely self-taught, mostly from books and technical papers.

I had (AFAIK) only one entry, which wasn't selected, which didn't surprise me. My big posts make extensive use of links (e.g. to explain vocabulary), especially to Wiki, and Open Lab is basically a book, with the selected blog posts printed on real paper. Handling links is presumably a tough issue, and posts that make extensive use of links aren't really all that appropriate.

Which brings me to the next subject of this post, which is blogging itself. (For reasons of time I'm not going to supply links for most of what I say.) Blogging started out (AFAIK) as mostly a way for people to put up links to interesting web pages, perhaps with a few comments. Much of it remains like this, but science blogging has evolved, in part, to something more sophisticated, including explanations of technical issues, and (including here) discussions at relevant tangents.

I was marginally involved in the early days of blogging, being a contributer to HotWired Threads, and one of the original contributers to NewsTrolls. NewsTrolls was an early blog set up by a HotWired Threads contributer called Pasty Drone, as HotWired Threads was winding its way down into obscurity.^[1], It focused on news items, and had a comments section much as modern blogs do. (This site has since vanished, as have the old Threads on HotWired.)

Even then, I was somewhat skeptical of this format, or rather I didn't see it as being optimum for what I wanted to write. My own purpose, usually, is to make a point based on and relating to peer-reviewed science, while most science blogging today is more a matter of explaining the technical aspects of peer-reviewed science for those who don't understand enough to get it from the paper itself.

However, Blogger makes a great platform for expressing myself without having to code the entire site by hand, so for the moment that's where I'm at.

Links

1. Educational Blogging by Stephen Downes

The Wheel Has Turned (No Spoilers)

2009-11-01T19:16:00.006-06:00

The latest book in Robert Jordan's Wheel of Time series, The Gathering Storm has appeared in B&N, although my last understanding is that it wasn't due 'till 11/03. I don't have time for a real review, and by the time I've created one everybody interested will probably have read the book, but herewith a few notes.

For those unfamiliar with the series, I have linked to the Wiki page, but haven't read it. It may not be completely reliable, as the series may be a contentious subject and Wiki sometimes has problems with these. However, it should give you a general idea. If you want to become familiar, I suggest starting with the first book in the series ("Eye of the World") and reading forwards. Don't rely on any sort of summaries. Watch out also for some half-sized books (for children) which split the first few volumes into smaller chunks. A careful perusal of the Tor website or Wiki should allow you to find which is which.

Jordan's posthumous co-writer, Brandon Sanderson, says in the preface, introduction, or whatever (I don't have the book with me as I write) that we should consider this the first 1/3 of the final book of the series ("A Memory of Light"), and I strongly agree.

He also mentions that he has written in his own style, rather than trying to imitate Jordan. I find the writing itself rather similar, however he (IMO) takes a different approach to simultaneity, with different scenes much more separated in time than Jordan. (I may be mistaken about this, I just don't have time to go back and double check. And in any case, this doesn't include the first and last chapters of previous books, whose scenes have always been somewhat out of sync.)

I found this book much more satisfying than the last few, in the sense that many more issues are being resolved than opened. This was to be expected, but I can confirm it.

I'm not going to discuss plot details, or even list which issues have been resolved, but I will say that it's my impression that there are far fewer surprises here than in previous books. That doesn't mean that any issues were resolved in precisely the ways I had anticipated, but that in general the resolution fit within my broader expectations.

I strongly recommend reading it if you're following the series, and I can say that IMO Sanderson is doing a good enough job that we can expect to enjoy the finalization of the series almost as much as if Jordan had done it himself.

Ardipithecus ramidus Illuminates Human Origins (Science Mag: Open Access)

2009-10-02T07:54:00.004-05:00

I'm really short on time, but readers need to know about the October 2 edition of Science Magazine, which:

presents 11 papers, authored by a diverse international team, describing an early hominid species, Ardipithecus ramidus, and its environment. These 4.4 million year old hominid fossils sit within a critical early part of human evolution, and cast new and sometimes surprising light on the evolution of human limbs and locomotion, the habitats occupied by early hominids, and the nature of our last common ancestor with chimps.

Science is making access to this extraordinary set of materials FREE (non-subscribers require a simple registration).

I haven't had time to read much of it yet, but what I've seen is very suggestive.

Carnival of Evolution 16 Is Up

2009-10-02T07:49:00.001-05:00

Here. A great line-up, including two from here.

Encephalon #76 Is Up

2009-09-28T08:18:00.000-05:00

Here.

Looks like a great line-up.

BTW, I'm really busy with outside projects right now, so big posts are going to be sort of thin on the ground for a while.

Energy and the Brain

2009-09-18T09:20:00.001-05:00

The questions of how much energy is used by the brain, especially its various parts, and how it's used are important. For one thing, our understanding of the brain depends strongly on functional magnetic resonance imaging (fMRI), which in turn has a number of built-in assumptions and open questions regarding how blood flow and nutrient concentrations relate to energy usage within the tiny regions (voxels) that it can resolve.^{[7] [8]} When dividing the brain into "parts" I'm talking not so much about areas or regions of the brain, as the microarchitectural constituents, such as axons, large and small dendrite branches, parts of the synapses on both sides of the synaptic cleft, and even astrocytes and other glial cells. (There's considerable debate regarding how much and what types of energy transfers take place between glial cells and neurons.^[8])

Thus, a very recent paper in Science,^[1] Energy-Efficient Action Potentials in Hippocampal Mossy Fibers (by Henrik Alle, Arnd Roth, and Jörg R. P. Geiger) provides an important resolution to an open question regarding energy usage in unmyelinated axons. They studied the current flows in axons of the Hippocampal Mossy Fibers, and demonstrated that the axons of these cells likely use about a third of the energy predicted by the standard notion, which is based on work going back to 1952.^{[13] [14]} The general applicability of this notion has been disputed, however, since at least 1975 based on early data^[11] on unmyelinated axons of different species obtained with radiolabeled K⁺.^[1]

I'm going to start with the implications of this finding, followed by a discussion of what Alle et al. did and didn't discover, followed by a brief summary of what they did to perform this measurement.

Implications of the Lower Axonal Energy Usage

I've previously discussed the various functional aspects of the brain, in terms of performing the calculations (computations) leading to its function. These include the general system of action potentials (APs) being fired in neurons, traveling along the axons to the pre-synaptic areas where they stimulate the release of neurotransmitters, which cross the synaptic cleft to stimulate currents in the post-synaptic areas in dendrites of other neurons, which currents in turn produce voltage changes that are transmitted to the soma (neural cell body), the axon hillock, and the Axon Initial Segment (AIS) which are the most common locations for the firing of new APs (primarily the AIS). I've also discussed the ways in which many calculations can take place beyond the simple determination whether/when to fire an AP, as well as the non-linear ways in which the dendrite behaves as an "active cable", rather than the passive cable used in simpler models of neural activity.

Now, in order to behave as an "active cable", the dendritic membrane has to have some level of on-going current that can be modified in a non-linear fashion in response to voltage changes. These currents, or rather the ion-pumping activity required to maintain (or recover) the concentration gradients that drive them, cost energy just as do the currents in the synapses and axons. We have general ideas how much total energy any region of the brain uses during various activities, and the reduction of how much we think the small, local, unmyelinated axons are using means there's more left over for the other functions, including membranes with "active cable" characteristics. ...

The Results of the Research

Let's start with the easy stuff. This study was done in the hippocampus, which is one part of the brain out of more than a hundred. We can't know for sure that similar energy-efficiency holds in any other regions of the brain until similar studies have been made for them. Similarly, this study was done in rats, and in principle we don't even know if the findings hold true for mice, much less monkeys or humans. Finally, these findings apply to only one kind of cell in the hippocampus. In principal it might not hold for the other types of cell even there.

Realistically, however, it's reasonable to assume that what holds in one place holds in all, at least potentially. Various studies of brain energy have suggested much lower values for axon energy usage,^[11] and we can assume that what evolution has done in one place, it can do in others, assuming some sort of selective incentive to reduce energy expenditure. And I think we can. (Ideally, there should be some scattershot studies of other cell types and regions, to verify the general principle. Hopefully this will offer opportunities for various researchers to get published, now that the cream has been skimmed off the discovery.)

Given the energy incentives for large-brained creatures, it seem likely that this energy efficiency evolved early in the lineages leading to mammals (and likely dinosaurs and birds as well, maybe independently). However, the rapid early expansion of the brain in Hadrocodium wui, to a point large even for modern mammals,^[15] may represent the first opportunistic use of some mutation allowing for this energy efficiency. (Studies of monotreme, bird, crocodilian, and other reptilian (and perhaps amphibian, depending on reptilian results) axon current flows are strongly indicated.)

In general, then, unmyelinated axons in mammalian brains can probably be assumed to be as energy-efficient as their needs for high speed will allow. Further research and modeling will probably give us a good idea what the trade-offs are, this can be expected to be a hot area of research for a while.

Now, let's take a look at what, specifically, was discovered.

I've included links to several discussions of how action potentials work, so I'm not going to try to cover everything here. Basically, there are several ion flows involved in the action potential in the axon, but primarily they are sodium (Na⁺) and potassium (K⁺), with the Na⁺ concentration much higher outside the cell than inside, thus creating a current when it flows into the cell (I_Na), and the opposite for K⁺ (which currents are abbreviated I_k). These two currents are in opposite directions, and if they occur simultaneously at any one spot along the axon they will cancel out, while taking up energy.

In the earliest research into such currents, which were done in the giant axon of the squid,^{[13] [14]} there appears to be considerable overlap. (This type of axon was used because its large size allowed researchers "to insert voltage clamp electrodes inside the lumen of the axon", even at this comparatively primitive stage of the technology.) The assumption was made that this overlap was general, even in mammals, although (as mentioned above) other research on unmyelinated axons suggested otherwise.^[11]

As it turns out, Alle et al. have discovered that there's much less overlap of currents than previously assumed because the I_K came mostly after the I_Na was complete. They also determined, through simulations, that

the observed degrees of charge separation are accompanied by comparatively low peak conductance densities, suggesting low numbers of channel proteins per area, which would minimize infrastructural costs for AP conduction.

Thus, not only are APs cheaper in energy costs than has been assumed, but the cost of producing the infrastructure is also lower.

How the Research Was Done

Alle et al. used a technique called patch-clamp recording to measure the currents found in the membrane of rat hippocampal mossy fiber boutons (MFBs). In patch-clamp recording, a small section of cell membrane is removed with a pipette, in this case from boutons, which are small enlargements of the axon containing the pre-synaptic portion of synapses. A voltage command was applied that duplicated "a previously-recorded AP wave", and the currents were measured.

The onset of K⁺ currents (I_K; Fig. 1, B and C, blue traces; n = 8) was significantly delayed compared to that of I_Na (106 ± 5 µs; P < 0.001), similar to results obtained from whole-bouton recordings (Fig. 1D, 115 ± 7 µs; P < 0.001, n = 8; P > 0.5 for patch versus whole-bouton recording). The resulting small overlap of inward and outward currents [Fig. 1, B (inset) and C] indicated a high Na⁺ efficiency and, accordingly, energy efficiency in hippocampal mossy fibers, contrasting with previous simulations of axonal APs and their underlying currents ([refs]).^[1]

Untangling the technical language, we see that the cell membrane of these particular axons responds to the voltage regime found in the AP with currents that barely overlap. This is the core finding.

There were also simulations:

To complement these results by a quantitative assessment of the Na⁺ influx as well as peak Na⁺ and K⁺ conductance densities (G_Na and G_K) underlying an AP propagating along an axon, we performed numerical simulations of APs. We used conductance functions (Fig. 2A) derived from recorded currents (Fig. 1) in a compartmental model of the mossy fiber ([ref]) to reconstitute propagating APs ([ref to supporting data]). Simulations resulted in AP waveforms and underlying currents closely resembling recorded APs and currents (Fig. 2B and fig. S1, A to D). The validity of our approach was further tested with independent predictions of the model, such as I_Na onset potential and AP propagation velocity, which both complied with experimental data (Fig. 2C and fig. S2).^[1]

These demonstrate that the values and timings of the currents involved, when incorporated into simulations, match the observed data.

They also analyzed the energy costs of the activity at the synapse that results from arrival of an AP, estimating that

the cost ratio of the mossy fiber AP itself to the downstream events (Fig. 4) has an upper limit of about 0.15 ([ref to supporting data]), shifting the emphasis of activity-dependent energy demand to downstream processes elicited by transmitter release, as suggested by in vivo work ([refs]).

IOW the APs require less energy, so there's more for other processes.

Alle, H., Roth, A., & Geiger, J. (2009). Energy-Efficient Action Potentials in Hippocampal Mossy Fibers Science, 325 (5946), 1405-1408 DOI: 10.1126/science.1174331

Links: I've included only the links called out in this leader. Not all of these links are called out in the text. Many are references taken from the featured paper. Use the back key if you came via clicking a footnote.

1. Energy-Efficient Action Potentials in Hippocampal Mossy Fibers paywall

2. An Energy Budget for Signaling in the Grey Matter of the Brain Open Access

3. The neural basis of functional brain imaging signals

4. The Cost of Cortical Computation Open Access

5. Hemodynamic Signals Correlate Tightly with Synchronized Gamma Oscillations Free Registration Required

6. Coupling Between Neuronal Firing, Field Potentials, and fMRI in Human Auditory Cortex Free Registration Required

7. What we can do and what we cannot do with fMRI

8. Metabolic and hemodynamic events after changes in neuronal activity: current hypotheses, theoretical predictions and in vivo NMR experimental findings Open Access Author manuscript

9. An Energy Budget for the Olfactory Glomerulus Open Access

10. Functional Trade-Offs in White Matter Axonal Scaling Open Access

11. Energetic aspects of nerve conduction: The relationships between heat production, electrical activity and metabolism paywall

12. Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics Open Access

13. The Optimum Density of Sodium Channels in an Unmyelinated Nerve paywall

14. A QUANTITATIVE DESCRIPTION OF MEMBRANE CURRENT AND ITS APPLICATION TO CONDUCTION AND EXCITATION IN NERVE may be open access, slow loading

15. A New Mammaliaform from the Early Jurassic and Evolution of Mammalian Characteristics Free registration required

Scientia Pro Publica #11 is Up

2009-09-15T15:23:00.001-05:00

here.

Nothing of mine in it, evidently my post Semantic Strait-Jackets in Science wasn't acceptable. As for why, I won't even guess, but it wasn't that late a submission.

But the line-up looks pretty good, I'd recommend a visit.

Encephalon #75 is Up...

2009-09-15T14:27:00.000-05:00

Here.

Nothing from here on it (nothing good ready), but there still look to be some pretty good posts.

Homeotic Mutationism

2009-09-14T18:26:00.003-05:00

The guest post a while back by Dr. Filler brought up the issue of "adaptationism" vs. "homeotic mutationism". It seems to me that this issue is an example of the simplistic use of formulas in science (which I recently decried) where a more thoughtful approach would end up without the controversy.

Summarizing from most of the various papers I read (see Links), the foundation of "adaptationism" is the assumption that the genetic variation on which Darwinian selection operates involves such small increments of change that they appear continuous. Mutation as a source of variation operates (in this model) almost independently of selection, adding new variation to the gene pool, while natural selection operates against the entire existing pool variation by altering the relative distribution of different alleles for genes with variation. There also seems to me to be a tacit assumption that variation exists in any direction (within "morphospace", see here for a discussion of morphospace), so that anytime there is a selective incentive for evolution in a particular direction, it will happen.

(Afarensis pointed me to the 1996 book Adaptation edited by Michael Robertson Rose and George V. Lauder, as discussing the current "adaptationist" program. Evidently, the "adaptationism" discussed by Dr. Filler, and the papers mentioned above, is what Rose and Lauder define as the "Old Adaptationism". This is, by all appearances, dead. The "new adaptationism" takes some account of the ability of mutations to be "large", as well as accepting the the reality of developmental limitations on variation.)

A Recently Generated Example of Homeotic Mutation

I'm going to (briefly) discuss a recent paper documenting an artificial homeotic mutation^[15], in which an entire homeotic gene was rendered non-functional, and the impacts to various developmental systems was analyzed. This is certainly not the first such experiment, however its recent provenance, and the widespread impacts to diverse systems including "thoracic, lumbar, and sacral vertebrae and in the pelvis, along with alterations in the bones and ligaments of the hindlimbs" and "a reduction in lumbar motor neurons and a change in locomotor behavior",^[15] make it an excellent example of the sort of mutations that underlie the concept of "homeotic mutationism".

Before we start, however, let's take a look at genes and how they work. Wiki defines a gene as "the basic unit of heredity in a living organism." This is fine as a functional definition, but the history of research into the subject has provided some excess baggage: some deadwood that needs to be cleared away. ...

I'm not going to even summarize the process by which DNA sequences are translated into proteins. I've discussed this in past posts, and Wiki has a good description here (including the larger articles they link to).

Figure 1: Summary level cartoon of the "central dogma" regarding transcription and translation from DNA sequences to proteins. (From Wiki)

Specifically, the "central dogma" has often been taken to mean that a gene consists of the portion of DNA that codes for proteins. This isn't actually true, according to Wiki:

The central dogma of molecular biology was first enunciated by Francis Crick in 1958^[ref] and re-stated in a Nature paper published in 1970:^[ref]
The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that information cannot be transferred back from protein to either protein or nucleic acid.

As you can see, this "dogma" applies only to the translation of DNA sequences into amino acid sequences in proteins. It says nothing about whether the gene is, by definition, limited to the protein-coding region.

A Local and Temporary Definition of "Gene"

For purposes here, I'm going to use a limited definition of gene: only for protein-coding genes of Eukaryotes.^A1 A gene is the DNA that codes for proteins, all the sequence that is transcribed with it, and all the control sequences that (in sum) determine when/whether that gene is going to be transcribed.

This is different from the more common (often unstated) definition of only the coding region. It includes all the introns that are transcribed to RNA and then removed by editing prior to the beginning of translation. It also includes all the control sequences by which its transcription is controlled. From the point of studying mutations, adaptation, and selection, this allows most of the mutations that affect development to be included within the gene, by definition.

Technically, a gene also should include the DNA sequences that, while not affecting transcription, are close enough to do so if they should mutate from a neutral sequence to one that impacts transcription.

Now, many genes code for proteins that perform simple metabolic and/or "housekeeping" functions within the cell. Others code for structural proteins, that are used to build the cellular skeleton. But the most important genes, from the point of view of controlling development, are those whose proteins contribute to the activation of other genes. The network of information handling these proteins are involved in constitutes a powerful and complex analog computer within the cell.

How do these proteins and their DNA interact? Basically, any protein that can interact on a sequence-specific basis with DNA is a Transcription Factor (TF). (Technically, TFs are enzymes, as are all proteins that can catalyze a chemical process of any sort. In addition, we should probably demand that the interaction with DNA have some significant effect.) TFs can work to enhance the rate of transcription, reduce it, suppress it entirely, or do any of the foregoing to the effects of other TFs. They do this by spending part of their time connected to the sequence(s) they act on, and while they do other parts of the molecule interact with other enzymes, creating a complex analog logic. (See my early post How Smart is the Cell? Part II: The Gene Activation network as an Analog Computer for a more detailed discussion of this, and links to more technical and peer-reviewed discussions.)

All this depends on the interaction between the TF and the "Transcription Factor Binding Sites (TFBS or "binding site") that interact with" the TF. Now, as I mention:

A TF can interact with many binding sites, and its activity with each site will be independent of the others, except that when it's present in relatively small amounts, there will be competition among sites for TF activity.

The interaction between a TF and its binding site depends on the specific sequence of DNA in the binding site. However, experiments with TF binding have shown that there are many sequences that will bind any particular TF, usually all very similar. By comparing these sequences, it's usually possible to find a consensus sequence that is very similar to all of them.

The consensus sequence will generally have the highest binding energy, that is it will stick tightest to the TF. However, other similar sequences may be able to bind to the TF, although with different behavior. A few example consensus sequences are found in table 2 from The Evolution of Transcriptional Regulation in Eukaryotes.^[10] This means that when there are multiple binding sites with slightly different sequences, they will have different binding energies, and the activity will be different for the same concentration of TF. Note also that there can be multiple TF's with similar (but non-identical) consensus sequences, so that different binding sites may bind to different TF's depending on the relative concentrations of the TF's.

The effect of each TF concentration on transcription rate will be generally analog. Although a high enough concentration will saturate any particular binding site, producing full-bore transcription (assuming it's an enhancer), lower concentrations will cause each TF/binding site activity to perform an analog calculation.

The previous post was concentrating on how the gene activation network makes up a complex analog computer, but here I'm going to concentrate on the way the various types of mutation interact with this computer.

The Effects of Point Mutations

Let's start with a simple point mutation, the replacement of one base in the DNA sequence by another. When this happens in a coding sequence, it may be "silent", coding for the same amino acid, or "neutral", coding for a different amino acid that, however, doesn't make much (or any) difference to the protein function, or it might have an important effect. In any event, it affects every interaction of the protein, one way or another (and to some extent or another). But a change to one of the binding sites only affects that specific interaction with the TF(s) involved. Many of these changes have a very small effect on binding energy (which, in turn, has a small effect on the transcription rate). Others have a larger effect, sometimes much larger, but only on the transcription rate of the one gene involved.

But what happens when there's a similar point mutation to the coding regions for a TF? Here, the mutation may have an effect on many, sometimes many hundreds of, interactions. If every binding site had the same sequence, the effect of a point mutation to the TF would be the same for all the "downstream" genes it affects. However, the actual sequences at the binding sites often vary, and a change to the TF could well increase the binding energy for some binding sites, while reducing it for others. Moreover, the magnitude of the change can also vary, with some being minor and others major. Finally, the results of these changes will (often) differ depending on how the specific transcription logic for each binding site fits into the overall computing network.

This, then, is the foundation for homeotic mutations. Not every mutation to a TF constitutes a homeotic mutation, but there are some TFs that are involved in hundreds (or even thousands) of transcription control operations, and when a mutation occurs to such a gene, the effects can be widespread, unconnected, and apparently random. This, specifically, is the type of mutation that Dr. Filler has hypothesized occurred when the ancestors of the Great Apes split off from other lineages around 20MYA.

Now, the number of bases involved in any TF/binding site interaction might be around 5-20. There are many possible mutations that could occur either to the binding site or the TF, but the effect of any change in binding energy will usually be limited to a single (scalar) change. The more different binding sites a TF interacts with, the more "dimensions" a mutation to the TF can make changes to.

Although the case is not a simple example, I should mention that several Hox proteins (the quintessential homeotic genes) act on the same consensus sequence, but with:

subtle, but distinct, preferences to DNA sites that contained variations of the nucleotides within the consensus motif. We further showed that Hox proteins varied in their relative affinities for DNA. These data demonstrate that closely related Hox proteins exhibit subtle differences in DNA binding specificities and affinities. These differences are likely to contribute to the selective interactions of Hox proteins with target DNA sites in vivo.^[11]

These aren't recent mutations, the hox genes have been evolving separately for over half a billion years, but they are highly conserved, with many specific genes (coding sequences) showing almost identical activity when mouse coding sequences are grafted into fruit flies in place of the native version, and vice versa.

What this shows, then, is that changes to homeotic genes can alter the binding affinity to a large number of different sequences, in different ways. A new homeotic mutation would probably be much "rougher" in its effects, at least until subsequent mutations to the binding sites "smoothed out" the effects, but such mutations could certainly occur even with a point mutation.

Effects of Other Types of Mutation on Homeotic Genes

Several other types of mutation need to be considered here. One type is where a section of code from another, related, gene gets grafted into the coding sequence in place of an original of similar length. This could well happen during DNA repair of a gene with many relatives, such as the Hox genes. (Specifically, the repair of a double-strand break through homologous recombination, which could potentially use a related gene as a template rather than the other copy of the original.)

Here, we potentially have the recombination of the part of the protein that interacts with one end of the consensus sequence with the part from another, related but not identical, protein that interacts with the other end. The result could be a gene with widely changed interactions with the various sequences it controls. Moreover, the "grafted in" section has undergone its own long evolution, creating its own system of binding energies with different sequence fragments. Although the mutation is "random" in the sense that a the new protein's affinities to the various sequences it controls will change in unpredictable ways, it's "random" within a very constrained space of possible changes.

Unlike point mutations, these mutations are capable of producing enormously organized suites of changes, although such suites will almost always be mal-adaptive. But not always, just almost always.

Another type of mutation also involves DNA repair, but this time instead of grafting in a homologous sequence from a related functional gene, the replacement sequence comes from a pseudogene originally created as a non-functional copy of this gene, which has been sitting in the genome accumulating random mutations for some time (ranging from very recent to somewhat older). The importance of this type of mutation is that several point mutations can accumulate without having any effect (because a pseudogene doesn't get expressed), until a short sequence is copied into the functional gene during DNA repair. As with most mutations, the very large majority would be mal-adaptive, but those that are viable can cross deep valleys in the "fitness landscape" that a working gene can't cross because any of the individual point mutations would be lethal or very mal-adaptive.

One more type of mutation must be considered, and that's a change to the control sequences of the homeotic gene itself. While such a change wouldn't affect the binding affinities between the homeotic gene and the downstream genes it affects, it could cause the gene to be expressed in places it wasn't previously, with all sorts of potential odd effects. Like the other types of mutation I've discussed, the vast majority of such mutations would probably be mal-adaptive, but the occasional adaptive one could produce homeotic effects.

There are other types of mutation that could produce potentially viable homeotic mutations, but the ones discussed are sufficient for an explanatory example.

An Artificial Example of a Homeotic Mutation

Now that we've examined just what a homeotic gene is, and how mutations to their protein coding can have such widespread effects, let's return to the example I mentioned above.^[15] Axial and appendicular skeletal transformations, ligament alterations, and motor neuron loss in Hoxc10 mutants by Sirkka Liisa Hostikka, Jun Gong, and Ellen M. Carpenter.

The specific gene involved is named Hoxc10. We must note that in mammals the hox genes are actually defined in four separate families, the result of "the ancestral vertebrate genome being twice duplicated in its entirety", or at least one complete duplication and one duplication of both hox families.^[16] Hoxc10 is part of the third ("c") family of hox genes, descended from the Hox10 gene of the original single string in the old pre-vertebrate chordates.

What Hostikka et al. did was create a version of this gene "producing a protein lacking the ability to bind to DNA."^[15] In mice where the allele was homozygous (where both chromosomes had this inactive allele), results included the following:

The lack of a functional Hoxc10 homeobox causes several homeotic transformations in the axial skeleton (Table 1, Figures 3 and 4). Wild-type C57Bl/6 mice typically have 30 precaudal vertebrae, with the more caudal vertebrae organized in T13L6S4 pattern, with thirteen thoracic vertebrae, six lumbar vertebrae and four sacral vertebrae [refs]. Eighty percent of the wild-type mice examined in this study exhibited this pattern, with the remainder of the animals showing some mild variation in the shape of the L1, L6, or S1 segments; these types of variations are within the range of normal [ref]. Hoxc10 mutant mice also have 30 precaudal vertebrae, but the patterning of the vertebral column is altered. Most Hoxc10 mutant mice (33 of 34 examined) show a partial to complete transformation of the thirteenth thoracic vertebrae, precaudal vertebra 20 (PC20) into a lumbar identity, typified by the reduction or complete loss of the thirteenth rib. By definition, thoracic vertebrae are those vertebrae with attached ribs; hence loss of the thirteenth rib suggests a posterior transformation of the most caudal thoracic vertebra into a lumbar identity. The most caudal lumbar vertebra (PC25) often undergoes a similar transformation into a sacral (S1) identity (Figures 3 and 4). The sacrum in wild-type animals is typically comprised of four vertebrae. The first two vertebrae, S1 and S2, have butterfly-shaped, fused transverse processes. The next two sacral vertebrae, S3 and S4, have transverse processes that are not fused, with S3 having butterfly-shaped transverse processes and S4 having club-shaped transverse processes similar to those seen on more caudal vertebrae (Figures 2 and 3). In Hoxc10 mutant animals, the fourth sacral vertebra (S3* in Figures 3 and 4) exhibits an intermediate shape between a normal S3 and S4, and there are usually five sacral-like vertebrae, three fused and two free. This suggests an anterior transformation of the first caudal vertebra into a sacral identity. This transformation restores the register of the vertebral column and thus there is no overall loss of precaudal vertebrae. In combination, these alterations produce a T12(T13/L1)L5S5 pattern in 94% of mutant mice. Heterozygous mice show several intermediate patterns, most commonly T13L5S5 (31.5%) or T12(T13/L1)L5S5 (38.9%), suggesting dosage compensation. The transitional vertebra, defined as the most anterior vertebra to show a lumbar rather than a thoracic articulation between the pre- and postzygapophyses [refs] is normally the tenth thoracic vertebra (T10), whereas in the homozygous Hoxc10 mutants the transition occurs at the ninth thoracic vertebra (T9) (Figure 4).^[15]

In addition to the changes to vertebrae:

The bones in the hip, the ilium, ischium and pubis, are constructed from independent condensations that grow together after birth. All three bones meet at the acetabulum, but the ischium and pubis also meet at the ventral edge of the pelvis. These two bones are angled 45° from each other on the anterior, acetabular end, and are connected by a cartilaginous bridge where they meet on the posterior side. This bridge undergoes calcification during puberty, and the pelvic apparatus is normally fully fused by eight weeks of age. In Hoxc10 mutants, the cartilaginous bridge forms normally, but the calcification process is delayed, leaving a prominent seam or indentation on the posterior edge of the pelvis, dyssymphysis ischio-pubica. In all mutant adults the bones touch each other but even in the mildest cases, a seam is visible unlike in the controls (Figure 5A, B; Table 2). The C57Bl/6 background strain has been reported to have high incidence of dyssymphysis, especially in females [refs], however, somewhat newer reports have claimed only 30% incidence which was lost when C57Bl/6 mice were crossed to another strain [ref]. To minimize differences attributable to genetic background, wild-type sibling controls were used for all experiments.^[15]

The hindlimbs were also affected:

There are several alterations in hindlimbs and hip joints in Hoxc10 mutants. During embryonic and early postnatal development, there are no visible skeletal defects in the hindlimbs. However, by four to six weeks postnatally, a bony ridge develops along the anterior longitudinal line of the shaft of the femur (Figure 5). A likely cause for the formation of this femoral ridge is the presence of an ectopic branch of the iliofemoral ligament. The iliofemoral ligament is a sheet-like structure on the anterior side of the femoral neck, acting as a part of the synovial capsule. Normally, the ligament joins the ilium anterior to the acetabulum of the hip joint to the intertrochanteric line of the femur. During development, this ligament expresses Hoxc10 (Figure 2C-F). The ischiofemoral ligament connects the dorsal aspect of the ischium to the femoral neck. In the mutant, the ischiofemoral ligament is visibly weaker than in the wild-type mice, and attaches more dorsally to the medial side of the rim. The iliofemoral ligament, on the other hand, has two femoral connections in the mutants: one normal connection that attaches as a part of the synovial capsule into the femoral neck and another that attaches onto the anterior shaft of the femur (Figures 5 and 6). This second ectopic branch attaches to and is part of the anterior femoral ridge. The point of attachment varies from just distal to the intertrochanteric line to halfway down the femur, likely affecting the extent of ridge calcification that varies between animals and progresses with age. This phenotypic attachment site variation likely drives the differences in the shapes of the femoral ridges of the mutants from prominent to moderate, reflecting additional stresses on the bone. The femoral ridges are found in all the mutants six weeks and older (Table 2). Histological study of the extra ligament shows an organized fibrillar structure, indicating no aberrant pathology (Figure 6C). Serial sections of newborns show the ligament attaching to the femoral shaft (Supplemental Figure 2), also seen in some newborn skeletal preparations as Alcian blue-stained material in the ridge area indicating cartilaginous material, likely sulfated proteoglycans, at the femoral end of the abnormal ligament (Figure 5F, G).^[15]

There were also effects on the nervous system:

Initial analysis of peripheral nerve projection patterns in Hoxc10 mutant embryos using anti-neurofilament antibody labeling suggested that there were no gross defects in the formation, appearance, and projection of spinal nerves in Hoxc10 mutant embryos. Motor and sensory projections into the developing hindlimb bud appeared normal as well (Figure 2). However, in light of alterations in motor neuron positioning in paralogous Hox10 gene mutants [refs] we decided to examine these neurons more carefully in serial histological sections collected from newborn animals. Serial 10 µm sections were collected from three wild-type and three Hoxc10 mutant animals. Lumbar segmental position was established as previously described [ref] and the number of motor neurons in the medial and lateral motor columns (MMC and LMC, respectively) in the L1-L4 spinal segments was counted. All motor neuron populations showed substantial reductions in Hoxc10 mutants (Figure 8). We further distinguished both medial and lateral components of the LMC; both components showed similar reductions in numbers of motor neurons. Despite the reduction in numbers of motor neurons, the distribution of these neurons appeared relatively unchanged, with MMC and LMCM neurons showing a peak in their distribution in segment L2 and LMCL neurons peaking in segments L3/L4. This suggests an absence of an anterior spinal segmental transformation, in contrast to results observed in Hoxd10 mutants and Hoxa10/Hoxd10 double mutants [refs]. These cell counts appear to reflect an absolute loss of motor neurons, as there is no evidence of compensation in one pool for losses in another.^[15]

Note that these changes are the result of complete elimination of DNA-binding functionality. If the mutation had made small changes to the affinity for all the possible binding sites (rather than setting them all to zero) any or all of the areas found in this study might have been affected, but in different ways. Of course, as mentioned above, the hox genes (in mammals) are a complex family of multi-duplicated genes, with similarities in affinities between members of the same family. Thus, mutations to Hoxc10 will interact with Hoxa10 and Hoxd10 (there's no hoxb10), with the possibility for much more complex results.

The Adaptive Fitness of Homeotic Mutations

The subject gets sort of sticky here. As with most mutations, the ratio of "adaptive" to "mal-adaptive" mutations is usually very small. However, the number of possible mutations is also extremely tiny compared to the "morphospace" within which such developmental changes operate. This is especially true because any change to the protein coded by a homeotic gene will have a specific effect on each possible sequence used in a binding site. OTOH, in the case of a normal homeotic gene (as opposed to the complex families of Hox genes), the only thing that really matters for any specific binding site is the affinity its sequence has for the TF. There can potentially be a number of different sequences for the same binding site (multiple alleles of the same gene, using my definition of gene) with essentially identical affinities for the old TF, that would respond differently to the mutant version. Thus, closely related species could have several, or even many, binding sites with different sequences that all act identically (between species) with the old TF, but react differently to the same mutation.

Indeed, such an effect doesn't even require different species. Since a mutation to a specific binding site is "silent" if it doesn't affect the affinity for the old TF, even a small population could have several different versions of the same binding site, with different responses to the same mutation. Since the gene for the TF will often be on a different chromosome from the "downstream" genes the TF controls (including their binding sites, which are usually near the coding region on the same strand of DNA), the mutant form will undergo the full "shuffling" activity of sexual recombination.

Mutationism and Adaptationism

Now, lets take a look at how all this mixes with "adaptationism". Many point mutations to binding sites will have a very small effect, either because they have a naturally small effect on affinity, or because the logic of the control network causes even a large change to affinity to have a small effect on overall phenotype. This is probably the most common source of "variation" found in typical animal morphology. Mutations with larger effects will occur, but will have a much larger chance of being mal-adaptive and thus being selected out of the population.

An important aspect, however, is that the only variation that this type of mutation can produce in the phenotype is that which can be caused by changes to the affinity of one or more binding sites for their TF(s). Thus, the morphospace within which the typical variation resides is much "flatter", ie. it has many fewer dimensions, than the changes that can be imagined for observed morphology. This places limits on how evolution can adapt a population for changing conditions: if a particular position in morphospace can't be reached via changes to binding site affinities, the form involved won't appear in the species no matter how strong the selective incentive.

What mutations can occur, sooner or later do, assuming a large enough population. They are then tested for "fitness" within the population, with mal-adaptive mutations quickly disappearing (with the rare exception of one that happens to be linked to a highly adaptive one). However, as the probability of a mutation decreases, the size of a "large enough" population increases. When the critical size for a mutation to likely occur becomes enough orders of magnitude larger than the typical population integrated over the entire lifetime of the species,^A2 the chance that that mutation will occur during the existence of the species in question becomes small, and the activity of evolution by natural selection becomes much less like the "adaptationist" model, and much more "mutationist", indeed, such mutations, many of which are homeotic, fit fairly cleanly into the old "hopeful monster" paradigm.

And it is here that we come to the point of the dispute. It can't be denied that many mutations produce very small changes in one or a few phenotypic characteristics. These, in the model I've discussed, will usually be changes to the control sequences rather than the amino acid sequence of the protein coded for. This means that the adaptationist models are certainly valid for evolution, both within species and to create new species. But the existence of homeotic mutations, and our modern understanding of how the various TFs and their binding sites combine with other aspects of cellular intelligence to drive the fetal development of the organism, make the "hopeful monster" paradigm just as valid, if in a substantially updated form.

When it comes to the many types of homeotic mutations that have such a low probability of occurring that there's, say, only a few percent chance of it happening during the lifetime of the species, we have pretty much left "adaptationism" behind, and are into the realm of "random creativity". In this type of scenario, the rare adaptive homeotic mutation can cause the origin of a new species, or higher level clade, if it occurs, but that occurrence is a matter of random chance. This is not to suggest that such mutations are in any way "directed", or that there are other forces than natural selection that determine the success of a particular homeotic mutation.^A3 Rather, the "inevitability" of any particular homeotic mutation has been totally falsified (again, only in the case of the very low-probability ones), and the course of evolution is basically determined by the random chance of which such mutations arise when.

We see, then, that the "debate" between "adaptationism" and "mutationism" is either a matter of emphasis, or the denial of one or another valid mechanism by extremist proponents of the other. Both are valid, and technically even the most "hopeful monster" oriented form of homeotic mutationism still depends on natural selection and adaptation to pick out the rare adaptive mutation from the much larger mass of mal-adaptive.

Hostikka SL, Gong J, & Carpenter EM (2009). Axial and appendicular skeletal transformations, ligament alterations, and motor neuron loss in Hoxc10 mutants. International journal of biological sciences, 5 (5), 397-410 PMID: 19623272

Appendices:

A1. only for protein-coding genes of Eukaryotes: The differences between Eukaryotes and Prokaryotes include major differences in how they use DNA: in Eukaryotes the coding section of each gene is usually isolated along with its control sequences, so that different genes can reside on different chromosomes. In prokaryotes, most coding sequences tend to be combined into operons, with many genes being controlled by the same (set of) control sequences.

In addition, there are, in both types of life, genes that code for ribozymes (strands of modified RNA that function as catalysts in the manner of enzymes). These are often combined into operons even in Eukaryotes, so they don't fit into the logic of my argument here.

A2. the entire lifetime of the species: This makes sense at a high level, however when you dig into the details it gets a little iffy. For the typical species that lasts a few million years, with a population of millions to billions, if the probability of occurrence of a mutation is less than 1/total number of members (over the entire lifetime of the species), there will be significant chance that it will never occur. If it is much smaller, then the chance of its occurrence at all becomes small as well.

Where things get complicated is for species that have very large populations, especially divided into many distinct sub-populations, and that last a long time, say an order of magnitude longer than the typical few million years. Here, "silent" changes to various binding site sequences will have enough time to accumulate and diverge among sub-populations and over time, so that the exact same mutation to a homeotic gene will have different effects at different times and in different populations. From an adaptive standpoint, these would count as different mutations, although the change to the DNA of the homeotic gene itself is identical.

A3. other forces than natural selection that determine the success of a particular homeotic mutation: As it happens, there are a number of mechanisms by which one copy of a chromosome, with all the alleles it carries, can be preferentially selected during oogenesis or spermatogenesis.^[14] I'm not going to discuss these here, although they cannot be ignored. See reference 14 for a more complete discussion.

Links: I've only included the link called out in this leader. Not all of these links are called out in the text. Use the back key if you came by clicking a footnote.

1. Adaptation from Leaps in the Dark Open Access

2. Mutationism and the dual causation of evolutionary change paywall

3. Climbing Mount Probable: Mutation as a Cause of Nonrandomness in Evolution paywall

4. Mutation-Biased Adaptation in a Protein NK Model Open Access

5. The concept of developmental reprogramming and the quest for an inclusive theory of evolutionary mechanisms paywall

6. WHAT IS EVOLVABILITY?

7. A framework for evolutionary systems biology Open Access

8. Saltational evolution: hopeful monsters are here to stay Open Access

9. The new mutation theory of phenotypic evolution Open Access

10. The Evolution of Transcriptional Regulation in Eukaryotes Open Access

11. Hox proteins have different affinities for a consensus DNA site that correlate with the positions of their genes on the hox cluster Open Access

12. Adaptationism by Peter Godfrey-Smith and Jon F. Wilkins (final draft: for the Blackwell Companion to the Philosophy of Biology. This draft has probably been peer-reviewed, but I'm not certain.)

13. Three Kinds of Adaptationism by Peter Godfrey-Smith (In S. H. Orzack & E. Sober (eds.), Adaptationism and Optimality, Cambridge University Press, 2001, pp. 335-357. This is not the published version, and may be prior to peer-review.)

14. Genes in conflict: the biology of selfish genetic elements By Austin Burt and Robert Trivers

15. Axial and appendicular skeletal transformations, ligament alterations, and motor neuron loss in Hoxc10 mutants Open Access

16. Extensive genomic duplication during early chordate evolution Open Access

Carnival of Evolution #14 is Up.

2009-09-03T11:32:00.001-05:00

Here.

Unfortunately, I lost track of schedules (got several other things going on), and didn't get anything submitted, although there are two good candidates. I'll submit them for next month, and see what happens.

Meanwhile, the ones that did get there are pretty good, check out especially the one about how the appendix isn't vestigial after all.

Scientia Pro Publica 10: A Late Announcement

2009-08-29T10:39:00.000-05:00

Find it here, unless you already did. (It's been there since the 19^th.)

I kept a close watch for the first few days, then started to slack off. It was originally supposed to be hosted by Greg Laden at Quiche Moraine, and that was where I looked. Even after the announcement (on the 18^th) that it would be published "tomorrow", I looked there. And didn't find it, and didn't find it, etc. It just never occurred to me to look back at Living the Scientific Life (Scientist, Interrupted) for updates, where I would have found the post itself.

If anybody was waiting for me to announce Scientia Pro Publica, sorry. But I suspect anybody really interested would have been Googling it, and found it before I did. But if you aren't interested, you should be. Lots of good stuff there.

Semantic Strait-Jackets in Science

2009-08-20T16:18:00.008-05:00

While working on an earlier post, I ran into an annoying issue: in synapses, the result of a surge of GABA or Glycine is called and IPSP, meaning Inhibitory Post Synaptic Potential. This remains true even when the effect is actually excitatory. This is annoying, but easy enough to live with (for me) as I tend to think in historic terms, especially with regard to words.

But it brought to mind an interesting point: science is full of terms and definitions that are obsolete, with research subsequent to naming and definition having rendered the specific names, and/or some of the assumptions that went into them, invalid.

The case in point makes a good illustration: the assumption that a particular synaptic action in response to an action potential is inhibitory is built into the name, and it takes an effort of will and memory to keep track of the various times that it might be (or is known to be) excitatory.

But wait! There's more...

Not only does this semantic confusion result in lost time and errors when somebody forgets to allow for all the naming exceptions, but it also tends to channel everybody's thoughts into an assumption that the result of an action potential at a synapse is either one or the other, and that's it.

The reality, especially with chloride currents, is much more complex. ... Even if a burst of GABA causes the membrane to depolarize, the equilibrium voltage (also called the "reversal potential") may be somewhere between the resting voltage and the action potential threshold.

Figure 1: Effect of Cl^- current with Equilibrium voltage at ~-62mV as an example. (Original. You may link to, copy, and or modify this image.)

In figure 1, we see just this situation. Compare with those from Axons and Chloride Currents, where the illustrated equilibrium voltages are either below the resting voltage (figure 2), or above the action potential threshold (figure 3).

Figure 2: Effect of Cl^- current with Equilibrium voltage at ~-73mV as typical for a pyramidal cell soma. (From Axons and Chloride Currents. You may link to, copy, and or modify this image.)

Figure 3: Effect of Cl^- current with Equilibrium voltage at ~-54mV as typical for a pyramidal cell AIS. (From Axons and Chloride Currents. ; You may link to, copy, and or modify this image.)

In figure 1, a strong Cl^- current will tend to depolarize the membrane, but only so far. If an EPSP based on sodium or calcium attempts to depolarize it further, the Cl^- current will have a shunting action that will tend to resist this depolarization. How the membrane responds, and whether an action potential is fired, will be a very complex problem.

The very name IPSP, then, tends to prejudice our minds, hiding the complexity of what's going on. Ideally, IMO, this current should be renamed "CPSP" for "Chloride Post Synaptic Potential". This name is neutral with respect to whether it will tend to depolarize or hyperpolarize the membrane, as well as calling attention to the fact that the result is more complex than simply that binary choice.

Of course, I doubt it's going to change soon. Big Science has become as institutionalized as the Roman Catholic Church was in Galileo's day, if not as centralized in its power, and pushing such a change through would probably take as much effort as redefining Pluto as not a planet. Rather, this particular semantic strait-jacket will continue to inconvenience and distract people who haven't learned to live with it, along with all the other obsolete terms and definitions of this type.

The biggest problem I have with this isn't the distraction and tendency to hide important details. Rather, there are two ways to approach names, in science and anywhere else: you can remember them in functional terms, linking the words of the name to their everyday meanings, or you can remember them as arbitrary symbols, strings of words that represent a particular thing completely independently of their everyday meanings. When the string of words that makes up a scientific name doesn't represent the same thing as what the name is used for, only the latter way of remembering is available (unless you want to load up your brain with a bunch of the history of science). Thus, IPSP doesn't stand for an actual hyperpolarization of the membrane (which is what the words actually mean), but for a current carried by chloride or potassium ions, regardless of its effect on membrane voltage.

This turns learning about science into a process of memorizing pointless and arbitrary names, that can't be deciphered in terms of the everyday meanings of the words that make them up. Not only does this interfere with the education and development of people who would make good scientists, but it makes the field more attractive to the sort of people who don't do creative thinking: all they want to do is memorize formulas and rituals, and spend their career following the rituals they learned in college. Such people don't, IMO, really have much to contribute to science.

Axons and Chloride Currents

2009-08-20T13:10:00.007-05:00

It's commonly assumed that synapses using GABA and glycine as neurotransmitters are inhibitory, that is when an action potential causes the release of (one or both of) these neurotransmitters (from the pre-synaptic side of the synapse) the result is a reduced chance that the post-synaptic cell will fire an action potential. However, this is not always true, there are several common circumstances under which these neurotransmitters appear to increase the chance of an action potential firing in the post-synaptic cell, as discussed in two recent papers to be discussed here. First, let's look at the mechanisms responsible for this reversal of the standard expectations, then I'll go over the two papers, then integrate the subject with some of my previous discussions regarding the transmission of analog data (besides action potential timing) along the first few hundred microns of the axon.

The role of Chloride Currents in Neural Communication

In a recent post I described the general relationship of various currents, ion channels, and voltage events (e.g. spikes and action potentials) in the neural cell membrane, but deferred discussion of chloride (Cl^-) currents because of their complexity.

The key item regarding any ion-carried current is the equilibrium voltage (also often called the reversal potential): that voltage (across the cell membrane) at which the electrical pressure driving a specific ion in one direction exactly balances the concentration-driven pressure in the other. The equilibrium voltage is primarily determined by the relative concentrations on either side of the cell membrane, so a change to either concentration can produce a change to the equilibrium voltage, and different concentrations across different parts of the cell (membrane) will result in different equilibrium voltages. (They will also result in a net ion diffusion, along with an energy cost to maintain it: see below.)

Figure 1: Action Potential Threshold and Directions of Depolarization and Hyperpolarization Relative to Figure 3 of A New Integrative Theory for Cortical Pyramidal Neurons. (From Figure 4 of the same post.)

As you can see from figure 1, the typical equilibrium voltage for Cl^- falls right into the range of typical "resting" voltages across the membrane. All of these are within about 40 mV of a typical action potential threshold, which is primarily determined by the nature of the specific voltage-gated Sodium (Na⁺) channels present in that piece of membrane. (See my discussion here for more detail.) Now, let's compare the effects of changing the Cl^- concentration inside the cell from that of the soma (body) of a typical pyramidal cell to that of the axon initial segment^[A1] (AIS: the first part of the axon after it leaves the axon hillock).

Figure 2: Effect of Cl^- current with Equilibrium voltage at ~-73mV as typical for a pyramidal cell soma.^[1] (Original. You may link to, copy, and or modify this image.)

Figure 3: Effect of Cl^- current with Equilibrium voltage at ~-54mV as typical for a pyramidal cell AIS.^[1] (Original. You may link to, copy, and or modify this image.)

As you can see, raising the equilibrium voltage for Cl^- changes the direction of the current and its effect. Rather than being inhibitory (hyperpolarizing), the chloride current is excitatory (depolarizing), tending to make the post-synaptic cell more likely to fire an action potential. Notice in this illustration (Figure 3) the equilibrium voltage is higher than the threshold for firing an action potential, so enough chloride current can "do the job" independently of help from depolarizing influences coming from the dendrites. This has actually been observed in experiments.^{[1] [21]}

As mentioned in A New Integrative Theory for Cortical Pyramidal Neurons, the normal concentration difference is just about enough to create an equilibrium voltage in the same range as the typical resting potential. This is because the concentration of Cl^- outside the cell is greater than that inside by just enough to counteract the resting voltage. If, somehow, a higher concentration of Cl^- is present on the inside of the membrane, the equilibrium voltage will rise, as shown in Figure 3 for the AIS.

Now, we can't just leave it that the inhibitory effects of neurotransmitters such as GABA and glycine can be reversed, we need to consider both the receptors (all types) and and the effects of changing the voltage under inhibitory conditions. ... (read the rest in the full post)

Let's start with Figure 2, when a big dose of GABA arrives at a synapse. The fastest-acting receptor(s) for GABA are the GABA_A receptors, in which the molecule that spans the membrane contains both a pore through which the Cl^- ions can pass, and a receptor region (outside the cell) that fits to GABA like a lock to a key, changing its shape (and the shape of the molecule), and allowing the pore to open. (A good discussion of this receptor may be found at The Versatile GABAa Chloride Channel Receptor Complex at Physiology physics woven fine. I'm not going to try duplicate this work, but in reading it just keep in mind that the author has not considered that the GABA_A receptor can sometimes be excitatory.)

Notice, though, that the difference in voltages is very small. This isn't as important is it might seem, because when the depolarizing activity of an excitatory synapse (a regular one using i.e. glutamate or acetylcholine) tries to raise (depolarize) the voltage towards the threshold, the greater difference in voltage drives a greater current, tending to prevent the voltage from going very far from the resting potential.

By contrast, a potassium (K⁺) current will pull the voltage much farther down, distinctly hyperpolarizing the cell membrane, not just at the synapse but a considerable distance away. This will become important later (below), because another GABA receptor, the GABA_B receptor, can cause K⁺ channels to open, having just this effect. Individual cells can express different mixes of receptors, and even the same cell can have different mixes in different parts of the cell.^{[27] [28]}

This isn't just true of receptors, either. Ion pumps can be localized, with massively different densities in different parts of the cell membrane (as can many other membrane proteins.^[27]

Now, let's look at the AIS, in Figure 3. Here, a big dose of GABA opens the pores in the GABA_A receptor in the same way as above, but it produces a distinct depolarizing current, pulling the membrane voltage, as always, towards its equilibrium voltage, which in this case actually happens to be higher than the action potential threshold. Thus, in this case the GABA can not only be excitatory, it can trigger an action potential. (Of course, if the post-synaptic cell also expresses GABA_B receptors, the effect will be much more complex: see below.)

Chloride Concentrations and Their Maintenance

What are the typical CL^- concentrations driving these different currents? I'm not going to go into the extra-cellular (concentration outside the cell) concentration, since they're the same for all parts of the cell. (Since different parts of different cells are bathed in the same local extra-cellular fluids.) Instead we'll look at the intra-cellular (concentration inside the cell) found by Khirug, Yamada et al., one of the papers we'll be discussing.^[20]

By determining the reversal potentials mediated by sudden release of GABA("E_GABA values of –59.4 ± 1.5 mV (n = 14), –65.8 ± 1.2 mV (n = 14), and –70.9 ± 1.5 mV (n = 10), respectively (Fig. 1)"^[20]), they could calculate the concentrations:

Assuming an intracellular pH of 7.2, the intracellular levels of Cl– ([Cli]) calculated on the basis of the above E_GABA values ([refs]) are 11, 7.9, and 6.0 mM [milliMoles, a measure of concentration] for the AIS, soma, and dendrite, respectively.^[20]

Of course these values are typical of only one type of cell (dentate gyrus cells (DGCs) of the hippocampus of mice and rats), but they give us some numbers to work with.

How are these concentrations maintained against the inevitable leaks and currents, which would normally push E_Cl^- towards the resting voltage?^{[20] [33]} There are two specific transporters involved (out of a large number used throughout the body): Both are members of a large family called cation–chloride co-transporters (CCCs), transmembrane proteins that transport a specific mix of ions in a compulsory group (all together or none). One is a potassium-chloride co-transporter (KCC): KCC2, while the other is a sodium-potassium-chloride co-transporter (NKCC): NKCC1. (The numbers are confusing, the "1" has nothing to do with the "2": the body also has KCC1 and NKCC2, although they aren't relevant to this discussion.)

KCCs, including KCC2, transport one K⁺ and one Cl^- together, which is plenty to maintain the type of potential seen in Figure 2. The K⁺ has a strong pressure "pushing" it out of the cell, and it will drag the Cl^- along with it. (Remember that since these ions have opposite charges, they represent currents going in opposite directions.)

NKCCs, including NKCC1, move one Na⁺, one K⁺ and two Cl^- together, which means they will go in the other direction because the very high pressure "pulling" Na⁺ into the cell will trump the pressure of the other three ions.

During development, most neurons express NKCC1, making GABA_A currents excitatory, which appears to be necessary for proper neural development.^{[2] [20]} Mature neurons appear to mostly express KCC2 in the soma and dendrites, which makes Cl^- currents hyperpolarizing. There has been some controversy over how the higher concentrations in the AIS were maintained, with the standard explanation being the absence of KCC2 in the AIS.

GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na–K–2Cl Cotransporter NKCC1

This paper, (by Stanislav Khirug, Junko Yamada, Ramil Afzalov, Juha Voipio, Leonard Khiroug, and Kai Kaila,) investigates the conflict between the point (noted above) that the inevitable leaks and currents would normally push E_Cl^- towards the resting voltage, and the fact that Cl^- currents in the AIS have been observed to be distinctly depolarizing, which means that the concentration must be maintained at a level such that E_Cl^- is distinctly higher than the resting voltage. A simple absence of KCC2, which would push E_Cl^- lower, wouldn't cut it.

First, by subjecting different parts of the same cell to bursts of GABA (with any GABA_B receptors blocked using "CGP55845A [(2S)-3-[(15)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl)-(phenylmethyl)phosphinic acid]"^[20]) and measuring the resulting equilibrium voltages, they demonstrated the different values of E_GABA for the AIS, soma, and dendrites. This may reasonably be assumed to be close to the value for E_Cl^-, with only the GABA_A receptors working.

Then, they did identical experiments similar to the one described above with both wild type mice (WT) and mutants unable to express NKCC1 anywhere(NKCC1–/–). The results:

The WT neurons showed an axo-somatic ΔE_GABA that was similar (5 mV) to the one described above in the Thy1–mGFP neurons with AIS, somatic, and dendritic E_GABA values of –61.3 ± 2.4 mV (n = 14), –66.0 ± 1.6 mV (n = 22), and –71.0 ± 2.0 mV (n = 16), respectively. Notably, in identical recordings from the NKCC1^–/– neurons, there was no axo-somatic E_GABA gradient; the values for E_GABA at the AIS and soma were similar, –70.5 ± 1.5 mV (n = 17) and –70.3 ± 1.5 mV (n = 18), respectively. However, a somato-dendritic ΔE_GABA similar to that in the WT neurons was still observed (dendritic E_GABA of –74.6 ± 1.7 mV; n = 15). These data indicate a key role for NKCC1 in the generation and maintenance of the chloride gradient that results in depolarizing GABA responses in the AIS of mouse DGCs and suggest that NKCC1 has no significant influence on dendritic E_GABA. Interestingly, the above observations are not compatible with the idea that the somato-dendritic E_GABA gradient is set by NKCC1 and KCC2. The putative transport mechanism underlying this gradient is not in the focus of the present work, but preliminary observations point to a role of a bicarbonate-dependent somatic transporter that accumulates chloride in the DGCs (our unpublished data). ^[20]

They have thus demonstrated, for two types of cells, the DGCs and "rat neocortical layer 2/3 pyramidal neurons", that the excitatory (depolarizing) action of GABA synapses onto the AIS is probably caused by the expression and localized targeting of NKCC1. They've also discovered another effect evidently not caused by NKCC1: the difference in Cl^- concentrations between the soma and dendrites. It'll be interesting to see what further research turns up in this direction.

Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex

This paper (by Gábor Molnár, Szabolcs Oláh, Gergely Komlósi, Miklós Füle, János Szabadics, Csaba Varga, Pál Barzó, Gábor Tamás) reports intriguing results from "complex events triggered by individual action potentials in the human neocortical network." Unlike previous research, they used slices of human brain with part of the small-scale network intact, and applied single strong spikes to a single cell and observed the result.

Before I go on with this, let me save a lot of readers the effort of digging into the paper over ethical concerns with this blockquote:

All procedures were performed according to the Declaration of Helsinki with the approval of the University of Szeged Ethical Committee. Human slices were derived from material that had to be removed to gain access for the surgical treatment of deep-brain tumors from the left and right frontal, temporal, and parietal regions with written informed consent of the patients (aged 18–73 y) prior to surgery over the last 4 y.^[21]

(Anybody wanting more information can use part of the above blockquote in a text search in the article, which is open access.)

I'm not going to spend further on the methods, or the details of the results, instead jumping to a more "high-level" discussion, starting with another blockquote:

Our results show that a single spike of a pyramidal cell in the human cortical microcircuit is capable of activating complex sequences of postsynaptic potentials lasting an order of magnitude longer than detected previously [refs]. The initiation and internally precise temporal structure of these event series appears to follow a stereotyped mechanism of spike-to-spike transmission traveling through a subset of synaptically connected neurons that seems to be conserved across several brain regions of the human cerebral cortex. The flow of downstream activation that follows the first-order spike of the trigger pyramidal cell is directionally controlled at two consecutive synaptic steps. Second-order spikes are triggered exclusively in GABAergic interneurons and not in pyramidal cells due to interneuron-selective EPSPs of enormous amplitude. In turn, second-order spikes in axo-axonic cells give rise to third-order spikes detected only in pyramidal cells, resulting in trisynaptic EPSPs in the network because axo-axonic cells do not innervate other GABAergic cells [refs]. Synchronized to the spikes in axo-axonic cells, second-order spikes in basket cells and possibly in other types of interneuron [refs] elicit hyperpolarizing effects reported here as disynaptic IPSPs.

What does this mean? The human brain, (or at least the parts of the neocortex investigated,) is a very complex network of cells with positive (excitatory) and negative (inhibitory) effects, in which a single spike applied to a resting network ends up producing a stereotyped mix of these effects. Basically, there is a "cascade" (a bad analogy, but...) of action potentials, starting with the artificially triggered

"first-order spike", followed by one or more
"Second-order spikes" in "GABAergic interneurons", including axo-axonic cells which have excitatory GABAergic synapses on the AISs of pyramidal cells, as well as "basket cells and possibly in other types of interneuron" which have inhibitory GABAergic synapses on the somas and dendrites of pyramidal cells, followed in turn by
"third-order spikes detected only in pyramidal cells, resulting in trisynaptic EPSPs [excitatory postsynaptic potentials] in the network",

that is there are inputs directly to still other pyramidal cells from three (or more) pyramidal cells that fire during the third stage of the "cascade". The third stage includes not only multiple pyramidal cells firing, but a suppressive effect on other nearby pyramidal cells from the action of the basket cells and other interneurons with inhibitory GABAergic synapses.

One of the key points, for our purposes, is that the "axo-axonic cells do not innervate other GABAergic cells", they terminate only on the AIS of pyramidal cells.^[34] This means that the very excitatory GABAergic synapses we've been discussing play an essential role in this network process.

Beyond Action Potentials

So far, we've covered the currents resulting from action potentials in GABAergic synapses terminating on the AIS. But regular readers here will probably recall The Analog Axon, where I concluded:

It's not a totally new discovery, of course, that some nerve cells use more analog types of communication than just action potentials.^[refs] Sensory nerves especially, often make use of analog calculations. Nevertheless, except for the sensory margins of cognition, the central nervous system is usually pictured as communicating through action potentials that carry only their relative timing as information. Over long distances, this is probably true.
However, a great many of the connections in the brain, including the neocortex, arguably the most important part of the relative expansion of the human brain, are within a few hundred microns, the distance discussed here.

This is particularly important for the pyrmidal cells involved in the "third-order spikes" mentioned above, where the axo-axonic input has set up varying chloride currents--varying both along the AIS and over time. These currents set the membrane voltage, often to a point substantially above (more depolarizing) the nominal "resting" voltage, with equally varying effects on the size, length, and shape of the action potential, in addition to their contribution to the probability and timing of firing the action potential in the first place. While over longer distances these variations will go away, short collaterals to nearby neurons will cary them. Studies on the fixing the membrane voltage at the soma have shown effects propagating over 400 microns (μ),^[15], and we can probably add the length of the AIS to similar effects generated by voltage changes there. Similar distances for propagating analog effects have been found in presynaptic hippocampal mossy fiber boutons,^[14] the output synapses from mossy fiber cells where:

Excitatory presynaptic potentials result from subthreshold dendritic synaptic inputs, which propagate several hundreds of micrometers along the axon and modulate action potential–evoked transmitter release at the mossy fiber–CA3 synapse.^[14]

Note that these effects in the dendrites have to cross the soma before they can extend "several hundreds of micrometers along the axon", presumably similar subthreshold synaptic inputs landing on the AIS would propagate farther.

How many synapses are we talking about to be affected by these inputs? From the research mentioned above fixing the membrane voltage of the soma:^[15]

Layer 5 pyramidal neurons, like other cortical neurons, give rise to a local high density of axonal connections to other pyramidal and non-pyramidal cells[refs] (Supplementary Figs 1, 4 and 7). Indeed, examination of the main axon and local axon collaterals of biocytin-filled layer 5 pyramidal cells from our slices revealed, on average, 155 (±79; n=14 cells) putative synaptic boutons within 0.5-mm of the cell body, and 269 (±152) putative synaptic boutons within the first 1mm(Fig. 4c and Supplementary Fig. 7). These values are probably a significant underestimate of local synaptic connectivity, owing to the cutting of axons and limitations of axonal staining using the slice technique (see Supplementary Figs 1 and 4).^[15]

This means that the AIS and short collaterals of each pyramidal cell can potentially act as an independent integrator of axo-axonic inputs, feeding a real-time analog output from hundreds of inputs^[31] to hundreds of outputs^[15] through the size, duration, and shape of action potentials, as well as sub-threshold changes that could affect the size of the transmitter release burst at the synapse. Moreover, these effects are tunable: addition of GABA_B receptors to a synapse could produce a longer-term (50-300 ms) K⁺ current counteracting the depolarizing effect when many bursts of GABA arrive within a short time.

Like many other recent discoveries, these add yet more complexity, and potential calculating power, to the overall activity of the brain. This is an effect that will be very difficult to model in the more traditional neural networks, hammering home yet again how we must not limit our ideas of the brain's ability by what current models and neural networks can do. There's more where that came from, and the next decade will almost certainly see increasingly complex and powerful models of what the brain can do.

Khirug, S., Yamada, J., Afzalov, R., Voipio, J., Khiroug, L., & Kaila, K. (2008). GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na-K-2Cl Cotransporter NKCC1 Journal of Neuroscience, 28 (18), 4635-4639 DOI: 10.1523/JNEUROSCI.0908-08.2008

Molnár, G., Oláh, S., Komlósi, G., Füle, M., Szabadics, J., Varga, C., Barzó, P., & Tamás, G. (2008). Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex PLoS Biology, 6 (9) DOI: 10.1371/journal.pbio.0060222

Appendix: You can use the back key to return to where you were, or click on the quoted text to return to the line with the footnote.

A1. "axon initial segment" There's no link to Wiki because, as of this writing, I couldn't find anything on Wiki discussing it. So herewith...

As mentioned above, the AIS is the first part of the axon, "from the narrow beginning of the axon to the onset of the myelin sheath" (often more than 200 microns (μ))^[35], or in unmyelinated axons "a variable distance, 4-5 μ." It has recognizable features:^[31]

The initial segment of the axon is unlike any other known process of the nerve cell, and in certain respects it is unlike any other part of the axon itself. In the idealized nerve cell it arises from the summit of a conical projection on the surface of the perikaryon, the axon hillock (Fig. 1). The surface of the axon hillock is bounded by a plasma membrane with the usual trilaminate structure, but near the apex of the hillock (Fig. 2) a thin, dark layer of finely granular material appears just beneath the membrane. In low-power electron micrographs this granular material gives the membrane a dense appearance, so that on superficial examination the plasmalemma seems to be reduplicated or thickened. But the undercoating is not really a part of the limiting membrane; instead, it is a thin layer of powdery densities, about 100 Å [Ångströms] thick, separated from the surface membrane by a clear interval of about 30 Å (Figs. 3 and 5). As its margins are not distinct, these measurements cannot be precise. The undercoating extends from the narrow beginning of the axon to the onset of the myelin sheath, where it ceases as abruptly as it began. In unmyelinated axons the undercoating extends for a variable distance, 4-5 μ. Where the axon originates from a dendrite, the undercoating has the same sudden onset and is accompanied by other changes (see below) in the internal structure of the process that signal the beginning of an axon.^[31]

The above text, and the figures it references, are in Reference 31, which is open access, although it's rather old.

Both the axon hillock and the AIS are distinct compartments within the cell, which can be independently targeted by distinct mixes of specific receptors, ion pumps, and all the other types of machinery the cell uses.^{[27] [28] [29]} Ultrastructurally:

In the axon hillock (Fig. 2) microtubules collect into bundles of three to five or more, which funnel into the initial segment and run parallel with one another throughout its length. Large initial segments have five or six such fascicles, while small ones may have only one. The number of microtubules in a bundle varies considerably but is probably characteristic of the type of neuron. In the Deiters cells of the lateral vestibular nucleus (Fig. 5) and in the motor neurons of the spinal cord, the number of microtubules included in a fascicle is usually three to five, and in the pyramidal cells of the cerebral cortex (Fig. 6) the number can reach 22. In the Purkinje cell of the frog, Kohno (13) found from 6 to 25 microtubules in a bundle, but in the rat the maximum
number we have found in this type of neuron is only 10-12.
In longitudinal sections the fasciculated microtubules in the initial segment often appear darker than the single microtubules in the rest of the nerve cell and its processes. This appearance is due only partly to overlapping of the microtubules in a bundle within the thickness of the section. In addition, each microtubule is surrounded by a cloud of fine fibrillar material that contributes to the general density of the fascicle. In transverse sections it can be seen that the microtubules are arrayed close together in a curving and sometimes branching line (Figs. 3, 4, and 6). Single or isolated microtubules are rarely encountered in the initial segment. Favorably oriented transverse sections show that the microtubules within the fascicles are bound together by thin, dark crossbars or arms (Figs. 3 and 6).
The bundling of the microtubules ceases abruptly at the beginning of the myelin sheath. Whether they continue down the axons as isolated microtubules or are replaced by new tubules beginning in this region could not be determined from the sections that we examined.
Although the axon hillock and the beginning of the axon fail to stain with basic dyes, clusters and rosettes of ribosomes do occur in the axon hillock and, in diminishing quantities, throughout the length of the initial segment. Apparently they are not numerous or concentrated enough to produce a basophilia that is recognizable in the light microscope. The ribosomes are usually, but not always, associated with a tubule or two of the endoplasmic reticulum. At the beginning of the myelin sheath they disappear while the endoplasmic reticulum continues in its agranular form throughout the axon.
Other cytoplasmic components of the axon, the neurofilaments, the mitochondria, multivesicular bodies, and various vesicles, all pass into the axon from the axon hillock without undergoing any distinctive change in their appearance or aggregation. Near the apex of the axon hillock the mitochondria, neurofilaments, microtubules, and endoplasmic reticulum all assume a remarkably parallel orientation as they funnel into the narrow initial segment.
It is common to find synaptic boutons attached to the surface of the perikaryon at the axon hillock, but they are unusual on the surface of most initial segments. For example, in sections through the initial segments of some 60 different Purkinje cells only one synapsing bouton was found. In contrast, nearly every section through the initial segment of the cerebral pyramidal cell shows an attached bouton (Fig. 7). No examples have yet been encountered of initial segments studded with boutons like the dendrites and perikaryon of certain cells.
In a few cases in which the apposition between an axon terminal and the initial segment was caught in a favorable plane of section, it was possible to see that the typical undercoating of finely granular material was interrupted at such sites and that the surface of the axon reverted to the appearance it normally has in the internodal segments. Only at the location of the "synaptic complex" or "active zone" was there a deviation from the normal, here resulting from the aggregation of fine filamentous material that formed the postsynaptic density. The typical undercoating of the initial segment resumed beyond the margin of the apposing terminal. If a neuroglial process was inserted between the terminal and the axon, breaking the apposition, the typical undercoating reappeared beneath it. In our material the number of cases in which we could clearly follow both the pre- and postsynaptic membranes was too small to allow us to generalize this description with assurance.^[31]

These "synaptic boutons attached to the surface of the perikaryon at the axon hillock" and "the initial segment of the cerebral pyramidal cell" are at the center of the primary thrust of this post.

The AIS is the most common site for an action potential to begin, followed by the axon hillock. As the general dendritic excitement (depolarization) increases, the site often moves back, first to the soma, then sometimes to the proximal dendrite(s).^[35]

Links: (I've only included the links called out in this leader.) Not all of these are called out in the text. Use the back key if you came via clicking a footnote above.

1. Excitatory Effect of GABAergic Axo-Axonic Cells in Cortical Microcircuits requires free registration

2. Cation–chloride co-transporters in neuronal communication, development and trauma paywall

3. Chloride is preferentially accumulated in a subpopulation of dendrites and periglomerular cells of the main olfactory bulb in adult rats paywall

4. Cluster Analysis–Based Physiological Classification and Morphological Properties of Inhibitory Neurons in Layers 2–3 of Monkey Dorsolateral Prefrontal Cortex Open Access

5. Output of neurogliaform cells to various neuron types in the human and rat cerebral cortex Open Access

6. A Population of Prenatally Generated Cells in the Rat Paleocortex Maintains an Immature Neuronal Phenotype into Adulthood paywall Is this one relevant?

7. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system paywall

8. A subset of periglomerular neurons in the rat accessory olfactory bulb may be excited by GABA through a Na⁺-dependent mechanism paywall

9. Channel behavior in a gamma-aminobutyrate transporter Open Access

10. Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance Open Access

11. Structure of intraglomerular dendritic tufts of mitral cells and their contacts with olfactory nerve terminals and calbindin-immunoreactive type 2 periglomerular neurons paywall

12. Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity paywall

13. Enigmatic Central Canal Contacting Cells: Immature Neurons in "Standby Mode"? paywall

14. Combined Analog and Action Potential Coding in Hippocampal Mossy Fibers Requires free registration

15. Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential

16. Long-Term Activity-Dependent Plasticity of Action Potential Propagation Delay and Amplitude in Cortical Networks Open Access

17. Information processing by graded-potential transmission through tonically active synapses

18. Enhancement of presynaptic neuronal excitability by correlated presynaptic and post-synaptic spiking

19. Recurrent excitation in neocortical circuits paywall

20. GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na–K–2Cl Cotransporter NKCC1 Open Access

21. Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex Open Access

22. Axonal GABA_A receptors paywall

23. Robust Short-Latency Perisomatic Inhibition onto Neocortical Pyramidal Cells Detected by Laser-Scanning Photostimulation paywall

24. Excitatory GABAergic Activation of Cortical Dividing Glial Cells paywall

25. GABA Transporter GAT1 Prevents Spillover at Proximal and Distal GABA Synapses Onto Primate Prefrontal Cortex Neurons paywall

26. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations

27. Compartmentalizing the neuronal plasma membrane from axon initial segments to synapses paywall

28. Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons paywall

29. The distribution and targeting of neuronal voltage-gated ion channels

30. Excitatory effects of GABA in established brain networks paywall

31. The axon hillock and the initial segment Open Access

32. Proximity of excitatory and inhibitory axon terminals adjacent to pyramidal cell bodies provides a putative basis for nonsynaptic interactions paywall

33. The cellular, molecular and ionic basis of GABA_A receptor signalling

34. Salient features of synaptic organisation in the cerebral cortex

35. From molecules to networks : an introduction to cellular and molecular neuroscience edited by John H. Byrne, James Lewis Roberts, chapter 17

Diagonal Postures & The Descent from Human to Ape

2009-08-17T12:30:00.003-05:00

Homeotics, Cladistics and the Triple Emergence of Closed Hand Gaits in Descendants of an Upright Ancestor of the Apes

Guest Post by Aaron Filler, MD, PhD, FRCS

If an upright bipedal ancestor evolved first, why would three of its descendant lineages abandon orthograde posture and restore quadrupedal gaits to their repertoire?

Firstly, we don't have to have an answer as to why it happened if that is indeed what happened. If it occurred, then it occurred whether or not we have proposed and accepted a post-hoc adaptationist explanation for it.

This week in PNAS, a paper from Tracy Kivell and Daniel Schmitt,^[9] reports on differences between the functional anatomy of knuckle walking of gorillas as distinct from the basis in chimpanzees, strongly supporting the idea that these are two similar but independently evolved locomotor complexes. They go on to argue that humans therefore did not evolve from a knuckle walking ancestor.

These authors have focused on significant differences in the carpal bones that underlie the two forms of knuckle walking. There is a long and heated history of publications in this area (see the Upright Ape^[6] for a more detailed discussion of the knuckle walking controversy). Kivell and Schmitt^[9] add significant new information about the mechanics and anatomy of knuckle walking as it relates to the very different carpal bone structure in the two lineages. This work does greatly strengthen the argument that there is no proven basis for making these two adaptations into a single shared change that should have been present in the group ancestral to hominins.

On an adaptive basis, one of the arguments most strongly advanced for the preference of closed hand gaits in various hominoids is that the tendons are shortened to result in a passive "hook" of the hand when the arm joints and wrist are extended. This is for the purpose of efficient suspension from branches during hand hanging and locomotion.^[14] However, in the light of the Humanian model I have advocated,^[6]^,^[7] there would be a multi-million year history of locomotion without hand/arm use and a behavioral reliance on use of the hands for carrying crude tools and small food objects. Closed hand gaits allow hominoids to hold objects in their hands as they locomote - it is easy enough for an adaptationist to explain the adaptive benefit of being able to carry during locomotion when you are in competition with an upright bipedal hominoid. Classical Darwinists often miss this point because of the focus on competition with other species members, but Stephen Jay Gould has pointed out the seemingly obvious importance of competition above the systematic level of the species.^[8] This is all about what upright bipeds and knuckle-walkers do on the ground when they compete for resources - and fight with each other - in overlapping territories.

The homeotic mutationist position that I have advocated (The Upright Ape,^[6] Homeotic Evolution of the Mammals^[5]) tackles the question from the perspective of genetic drive and adaptationist fine tuning. The starting point is the demonstration that the Moroto vertebra demonstrates a truly remarkable transformation of the vertebrate body plan.^[5] In most mammals and indeed in most vertebrates - the main dorso-ventral body plane division is placed ventral to the neuraxis, but in a "hominiform" clade that includes hominins, some extant apes, Morotopithecus, Pierolapithecus, Oreopithecus, Orrorin and Sahelanthropus the body plane is shifted to a position dorsal to the neuraxis in the lumbar region.

A number of anatomical transformations in serial homology accompany this change and all of them appear at 21.6 million years ago in Morotopithecus. These include a "box-like" cross section of the lumbar transverse process as opposed to the more standard mammalian flat element and this appears to be evidence of bipedal rather than bimanual orthogrady - e.g. standing and walking rather than arm swinging. The anatomical basis of upright posture in modern humans is very clearly due to this transformation and it is fully present in Morotopithecus. Because of this, I have argued that this feature is the basis of a hominiform clade that separated from the proconsuliform hominoids very soon after the first emergence of hominoids in the early Miocene.

Sudden major transformations of this type are the province of mutationist^[17] rather than adaptationist evolutionary progression and are best suited to changes in the major morphogenetic genes such as the homeotic genes. The prime irrefutable example that challenges traditional evolutionists who refuse to understand the implications of modern morphogenetics is the origin of the vertebrates from the invertebrates. Invertebrates have their digestive tract dorsal to their neuraxis, while vertebrates have the neuraxis dorsal to their gut. Invertebrates develop the mouth from the blastopore, but vertebrates develop the anus from the blastopore. To get from the invertebrate body plan to the vertebrate body plan, you have to flip dorsal for ventral and anterior for posterior. An adaptationist argues that there were selective adaptive pressures that gradually turned the proto-vertebrates a few degrees at a time over millions of years. The morphogentic mutationist realizes that this is completely ridiculous and that - as the genes show - the readout gradients in the embryo got flipped.

Vertebrates with the dorsal neuraxis and "aboral" blastopore emerged in abrupt single generation transformations that led to a revolutionary new body plan. In Morotopithecus bishopi we see a similar morphogenetic revolution and the result is the proto-human that does not use its hand or arms to locomote. This most likely occurred in a single generation. A quadrupedal proconsulid-like ape mother and a bipedal orthograde child that was our clade founder once its descendants were isolated by a chromosomal speciation event.

I point out in the Upright Ape^[6] that every fossil hominoid species in the hominiform group for which we have post-cranial fossil evidence appears to be an upright adapted form and that there is no evidence yet of any knuckle walkers. The accepted position has been that humans evolved from knuckle walkers around 5-6 million years ago even though there has never been any evidence for this at all. The contrary position that I have advocated is supported by all the evidence from all of the five separate genera of hominiform hominoids known with post-cranial evidence from before the chimp-human split, distributed across time from the 21 to 5 mya, yet my position is the one that has been considered radical.

The general dictates of science are that more credence should be given to a theory with a variety of elements of supporting evidence and less credence to a theory that fits expectations but for which evidence has not yet been found. There are numerous objections to the Humanian Model - a blog I wrote on this subject on Anthropology.net drew nearly 20,000 views and attracted scores of comments making up a good mix of hostile and supportive reactions. However this suggestion has had a very significant impact (Science Daily, blog on afarensis, blog on scientific blogging, MSNBC) because of the strength of the evidence. It was also well received when presented at the 2008 meeting of the American Association of Physical Anthropology^[7] and was addressed specifically in presentations others - who reached conclusions consistent with the components of the Humanian Model.^[15] David Pilbeam - past Chairman of Biological Anthropology at Harvard - wrote the foreword for the Upright Ape.^[6]

Although I first laid out the case in 1986 in Axial Character Seriation in Mammals (republished in 2007),^[3] the publication of my 2007 books and papers coincided with the publication of work by Thorpe^[19] and Crompton^[2] arguing for a upright climbing antecedent for our terrestrial bipedal lineage. There have been three more new hominoid species reported since mid-2007,^[18]^,^[12]^,^[10] but none of these finds has included significant new post-cranial fossils. However, analysis of spinal evolution by Rosenman and Lovejoy^[15],^[16] is consistent with the Humanian model, an analysis of hand bones from Hispanopithecus laeitanus has demonstrated no sign of knuckle walking,^[1] and now the new report from Kivell and Schmitt^[9] on knuckle walking adds yet more weight to the non-Troglodytian models (no knuckle walking for the human ancestor).

Various studies show the inefficiency of chimpanzee bipedal walking and argue that only by a series of modifications could we arrive at the efficiency of the bipedalism of extant humans.^[13] However, this assumes that the common ancestor of chimpanzees and humans walked bipedally the way a modern chimpanzee does when a more correct scenario is probably that the common ancestor walked more as we do - and that its ancestors already had a 15 million year career of minor adaptations improving the effectiveness of bipedal gait.

In the Upright Ape,^[6] as well as in the Homeotic Evolution of Mammals^[5] and a paper on later Emergence and Optimization of Upright Posture for bipedalism,^[4] I update the original (1986)^[3] hypothesis by pointing out that the best way to view the locomotor specializations of modern orangs, chimps and gorillas is as examples of "diagonograde" posture. The basic hominiform spine - due to a homeotic mutation - is defective in that it loses the basic mechanical structure that supports the horizontal or pronograde spine in most mammals. This is what occurred in Morotopithecus and has never been restored. In most hominiforms, we retain a very flexible lumbar spine with five or six lumbar vertebrae. However in the orang, the chimp and the gorilla, the lumbar spine is dramatically shortened - to as few as three lumbar vertebrae and independently evolved bony stops that limit hyperextension of the non-orthograde spine appear - each quite independent and different in those three lineages.

Russell Tuttle^[20]^,^[21] showed that Orangutans do not knuckle walk - they fist walk. Owen J. Lewis^[11] showed that there was no clear shared anatomical basis for knuckle walking in the hominoid wrist (see Upright Ape for numerous references). Kivell and Schmitt^[9] have now showed that there are indeed two very distinct functional anatomical patterns for knuckle walking that distinguish chimps and gorillas.

So...if a series of hominiform hominoids share the long flexible lumbar spine that can't function usefully in pronograde or diagonograde postures, if all of these genera of hominiforms demonstrate anatomical features for support upon pelvis below rather than by suspension, and if the orangs, chimps and gorillas have independently evolved short stiff lumbar spines and closed fist diagonograde gaits, then what stands against a Humanian model of human evolution?^[6],^[7] Certainly there is a mountain of writing, publications, textbooks, theory and belief against it - but there is no actual scientific evidence to support anything other than an upright ancestor for the extant apes and humans.

I have further tried to look closely at what we mean by the word human (OUP blog: Redefining the Word "Human" - Do Some Apes Have Human Ancestors?). As I detail in the Upright Ape, we have Sherwood Washburn to thank for our anthropological definition of the word human and it is basically a hominoid that is bipedal and upright. Clearly, when we look at that century in the early Pliocene that immediately followed the speciation event that sealed the chimp-human split we would now have "humans." These humans would have a brain size no different from a chimp, tool use no different from a chimp, and communication no different from a chimp. The assumption has been that the common ancestor of chimps and humans would look like a chimp - an obvious "ape" - however, what if the common ancestor looked pretty much like the early humans. What if it is the human lineage that retains the primitive traditional hominiform body plan that has been around since the time of Morotopithecus?

I think we all know what we mean by "early human" - they have our basic body form but have smaller ape-like brains, shorter legs, a bigger set of jaws and teeth, and a big toe that spreads out further from the other toes than ours does now. Since the Oxford English Dictionary is probably the best forum for this question, it is on the OUP blog that I placed my piece on redefining the word "human".

From the point of view of cladistics, we really can't use the term "apes" anyhow since this does not form a monophyletic group. From that perspective, we would have to include humans as apes. In fact when you look at the actual sequence of events among the hominiforms and extant apes, "humans" came first, but then the cladists would have us calling the extant apes "humans" and that is not what anyone means. Hominiforms is a good cladistic term for the humans and extant apes. The word human - including early humans and proto-humans - is a good term under Ernst Mayr's view of biological naming in systematics (see discussion in the Upright Ape). We can also say Hominiforms of human body plan (HHBP). All of these issues arise because systematic diversification (speciation) does not necessarily coincide with morphological diversification - some primitive body plans are more effective than the modifications that appear in some descendants.

This is the specific point that Ernst Mayr attacked most specifically in challenging the Hennigian paradigm. In cladistics, whenever a new species arises, we have two daughter species and we say that the parent species is now extinct. Mayr felt that the typical situation was that you had a large slowly evolving population that occasionally emits a speciated branch with a subset of the genetic variability of the parent species. He felt it was biological nonsense to say that a species was now extinct if the genetic makeup of the parent species and the major daughter species were identical.^[22] In our situation - we would have a large parent species of human form out of which a small group becomes isolated that leads to the chimpanzees. We agree that the post-split group that is bipedal is now "human" but the pre-split group (from the century before the speciation event) is effectively identical. That pre-split group should be called "human" as well and then we have a human group ancestral to an extant ape lineage - at least in that situation.

One thing that all the naming and systematics logic does not affect is the apparent fact that the immediate ancestors of the all the extant clades of apes & humans had the appearance of modern humans in their body plan.

So we have hominoids that share a modified Y-5 molar and which includes the pronconsuliforms and the hominiforms. The hominiforms are basically upright and of human body form - or humanoid. From the early Miocene to the present, there has always been a lineage of upright primarily bipedal hominiform hominoids whose body plan is of human aspect. In essence these are creatures that don't use their hands and arms for locomotion.

Across time, various groups branch off that are more suited to ecologies and locomotor arenas where humans don't compete as effectively - that is because it has always been difficult for nonhuman-like hominoids to compete against those with human form. The proconsuliforms long since went extinct and the others have not succeeded sufficiently to leave any post-cranial fossils. Meanwhile, the upright bipedal hominiforms with a body plan of human aspect have left an increasingly abundant fossil record that spans 21 million years. They were not stooping forward and they may have been seen occasionally in trees (see my video of Siamang bipedalism and human brachiation: Hominiform Progression on You Tube, in high res on Vuze or as an iTunes podcast). At any point during this time span, if you were to encounter a hominoid it would most likely have been an upright bipedal species that when seen from a distance looked...well... human.

Kivell, T., & Schmitt, D. (2009). Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0901280106

References:

1. Almécija S, Alba DM, Moya-Sola S, Köhler M. Orang-like manual adaptations in the fossil hominoid Hispanopithecus laietanus: first steps towards great ape suspensory behaviors. ProcRoySocB 274:2375-2384 (2007) Open Access

2. Crompton RH, Vereecke EE, Thorpe SKS. Locomotion and posture from the common hominoid ancestor to fully modern hominins, with special reference to the last common panin/hominin ancestor. J Anat 212(4):501-543 (2008) Open Access

3. Filler AG. Axial Character Seriation in Mammals: An Historical and Morphological Exploration of the Origin, Development, Use, and Current Collapse of the Homology Paradigm. Brown Walker Press, Boca Raton, FL, (2007).

4. Filler AG. The emergence and optimization of upright posture among hominiform hominoids and the evolutionary pathophysiology of back pain. Neurosurgical Focus 23(1):E4 (2007).

5. Filler AG. Homeotic evolution in the Mammalia: Diversification of therian axial seriation and the morphogenetic basis of human origins. PLoS ONE 10(e1019) (2007). Open Access

6. Filler AG. The Upright Ape: A New Origin of the Species New Page Books, New Jersey, July (2007).

7. Filler AG. A Humanian Model of Human Evolution: Evidence that habitual upright bipedality is a synapomorphy that defines a hominiform clade of hominoids including humans and all extant apes. American Association of Physical Anthropology, 77th Annual Meeting, Columbus, Ohio April 10, 2008. AJPA 135 (S46): p.96 (2008)

8. Gould SJ. The Structure of Evolutionary Theory. Cambridge, Mass., Belknap Press of Harvard University Press (2002).

9. Kivell TL, Schmitt D. Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor. PNAS (2009). paywall

10. Kunimatsu Y et al. A new Late Miocene great ape form Kenya and its implications for the origins of African great apes and humans. PNAS (104) 19220-19225 (2007). Open Access

11. Lewis OJ. Functional Morphology of the Evolving Hand and Foot. Oxford/New York, Clarendon Press ;Oxford University Press. (1989).

12. Pickford M, Coppens Y, Senut B, Morales J, Braga J. Late Miocene hominoid from Niger. C.R. Palevol 8:413-325 (2009). paywall

13. Pontzer H, Raichlen DA, Sockol MD. The metabolic cost of walking in humans, chimpanzees, and early hominins. J Hum Evol 56:43-54(2009).

14. Preuschoft H. Mechanisms for the acquisition of habitual bipedality: are there biomechanical reasons for the acquisition of upright bipedal posture? J Anat 204(5): 363-84. (2004). Open Access

15. Rosenman BA, Lovejoy CO. Developmental anatomy of the hominoid lumbar transverse process: a comparative anatomical framework for examining lumbar natural history in early hominids. American Association of Physical Anthropology, 77th Annual Meeting, Columbus, Ohio April 12, 2008. AJPA 135 (S46): p.183 (2008).

16. Rosenman BA, Lovejoy CO. Relative lumbosacral transverse process length in extant hominoids and australopithecines. American Association of Physical Anthropology, 78th Annual Meeting, Chicago, IL April 3, 2009. AJPA 138 (S48): p.183 (2009).

17. Stoltzfus A. Mutationism and the dual causation of evolutionary change. Evol Dev 8: 304–317. (2006). paywall

18. Suwa G, et al. A new species of great ape from the late Miocene epoch in Ethiopia. Nature 448: 921-924 (2007). paywall

19. Thorpe SKS, Holder RL, Crompton RH. Origin of human bipedalism as an adaptation for locomotion on flexible branches. Science 316: 1328-1331 (2007). requires free registration

20. Tuttle RH . Knuckle-walking and knuckle-walkers: A commentary on some recent perspectives on hominoid evolution. Primate Functional Morphology and Evolution. R. Tuttle. Chicago, Mouton/Aldine: 203-209. (1975).

21. Tuttle RH. Knuckle-walking and the problem of human origins. Science 166(908): 953-61 (1969). paywall

22. Wheeler Q, Meier R. Species Concepts and Phylogenetic Theory : A Debate. New York, Columbia University Press. (2000).

Encephalon 74 is up

2009-08-17T11:04:00.000-05:00

Here.

Lot of good articles there. You'll probably want to check it out.

A Big Boost for a Revolutionary Theory

2009-08-13T16:18:00.001-05:00

One of my more favorite reads was Aaron Filler's Upright Ape: A New Origin of the Species^[3], shortly after it was published. The suggestion(s) regarding human evolution were attractive and revolutionary, while the discussions of homeotic mutations and their mechanisms (based upon peer-reviewed work^[4]) were enlightening and form part of the foundation of my own approach to understanding how mutation, development, and Darwinian selection work together (a subject I haven't blogged much about although it underlies much of my writing here).

Filler's primary suggestion is that the main stem lineage of the Great Apes has been walking upright since shortly after it diverged from the ancestors of the ancestors of the gibbons and siamangs due to a homeotic mutation that modified the spine to give it the potential to support an upright stance for long periods, something the gibbons and siamangs lack. (Although they can and do walk upright, both in the canopy and on the ground.) One of the implications of this theory is that the common ancestor of humans, gorillas, chimpanzees, and bonobos walked upright, and that knuckle-walking behavior evolved independently in the lineage leading to gorillas from that leading to chimpanzees and bonobos.

Figure 1: Example of the detailed anatomical discussion of the proposed homeotic mutation that lead to the human/great ape backbone structure. Click on image to see illustration and caption at the book's website. (From Reference 3, figure 9-5.)

Now, in the advance online Early Edition of PNAS, we find Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor^[2] (by Tracy L. Kivell and Daniel Schmitt), unfortunately behind a paywall, that describes research thoroughly undermining the notion that humans evolved from a knuckle-walking ancestor. Let's look at the research first: ...

What Kivell and Schmitt did was examine the "features most commonly thought to reflect knucklewalking behavior in the African ape wrist", in terms of their occurrence and development in many primates, and especially gorillas as well as chimpanzees and bonobos. They found "(i) that most gorillas lack key features that have been assumed to be critical for limiting extension of the wrist during knuckle-walking ([refs]), and (ii) these features are found in monkeys that use a variety of different hand postures and substrates."

Assuming that such features are necessary (or highly desirable) for knuckle-walking, we should find them emphasized in gorillas, and at earlier ages, since gorillas are larger, thus putting more stress on the bones of their hands during knuckle-walking, and normally start earlier during development. Instead:

In addition, the ontogenetic analysis shows that the features of the scaphoid that are assumed to be essential for knuckle-walking ([refs]) are not only inconsistently developed in Gorilla, but, when present, do not appear relatively earlier in development in gorillas (Table 2). Therefore, using the traditional functional interpretation of these features ([ref]), it would appear that the Gorilla radiocarpal joint may be actually less, rather than more, stable in extension throughout ontogeny compared to Pan.

The mention of stability during extension of the radiocarpal joint (bending back the wrist) leads to the next important feature of this report: the proposal that the method of knuckle-walking used by gorillas is different from that of chimpanzees and bonobos.

We propose that Gorilla uses a relative ‘‘columnar’’ forelimb posture during knuckle-walking in which the hand and wrist joints are aligned in a relatively straight, neutral posture compared to the more extended postures adopted by Pan (Fig. 3). Animals using a relatively columnar wrist and hand posture would have carpal joints that are in line with the hand and forearm, similar to limb joint position in large graviportal animals such as elephants ([ref]). Supporting loads directly over more vertically-oriented forelimb joints during support phase explains the absence of posited bony adaptations to bending loads in gorillas and also permits more mobility at the joint ([ref]). By contrast, Pan, which exhibit extended wrist postures (Fig. 3), will experience higher bending loads. Thus Pan carpal bones have relatively prominent osteological features that have traditionally, but mistakenly, been interpreted simply as features associated with knuckle-walking in general rather than with a specific posture. The notion that Pan and Gorilla use different wrist postures is consistent with the morphometric data presented here. Although this hypothesis has yet to be explored in detail with videographic data, this idea is further supported by previous research showing that Gorilla exhibits increased wrist mobility compared to Pan ([ref]), a more hyperextended elbow joint ([ref]) and relatively equal length of rays 2 through 4, which creates a larger, more stable area over which to disperse axial loads ([ref]).

Imagine the difference between doing push-ups on your fists and on a steel bar you've got your hand wrapped around with your wrist bent back. This is sort of what the difference is, but only sort of. Unfortunately, their "figure 3" is behind a paywall, but the important takeaway is that there is a difference in mechanism, the details of that difference, while important, aren't necessary to the wider implications.

Kivell and Schmitt have provided very strong support for the idea that knuckle-walking works differently, is used differently, and probably evolved independently in these two lineages. A less technically oriented discussion (than the paper) is provided by Science Daily^[1], I'm not going to try to replicate their work. (afarensis, FCD is not really convinced, I've discussed Filler's theory in comments on his (old) blog, and I've expanded and modified some of my arguments there in this post.)

Support for the Upright Ape

Instead, I'm going to discuss how this new research relates to the "Upright Ape" hypothesis. One key hypothesis here is that the homeotic mutation to the spine "pre-adapted" it to support the upper body when standing, walking, or running upright. I won't go into the details, but with this adaptation in place, we need to ask precisely why any possessor would go in for knuckle-walking. The answer is that the requirements of brachiation (swinging from the arms) include suppressing a twisting movement between the hips and the shoulders, a need that grows greater with greater size (mass). An ancestral "Great Ape" weighing no more than a typical gibbon might have found this movement easy to suppress, but a larger ape that depended on brachiation would have been under some selective pressure to suppress this movement.

(Another possibility, IMO, is that the lumbar structure of gibbons has actually become adapted to use the springy structures of the lumbar transverse process (LTP) to provide energy storage from/to this twising moment, which in Great apes must be suppressed by muscular action at the cost of energy. AFAIK no research has been done into this possibility. I'll mention that the springy structures involved are used in most mammals to counter the drop of the belly, allowing it to be suspended during walking and storing energy during running/leaping, while in Great apes it tends to counter the forward droop of the upper body while standing upright (because it has been moved dorsally of the center of flexion (bending) of the backbone by the homeotic mutation). For more detail, I must refer you to the book,^[3] I just don't have the expertise, and haven't done the detailed research, to attempt it. Thus I must also leave my suggestion regarding the gibbons as a possibility, until I find research (if any) into the details of how these structures work during active brachiation.)

Filler makes the case that the long hip structures and functionally short lumbar structures in African Great Apes represent adaptations to this selective pressure, and then goes on to argue that there are enough differences that this adaptation was probably made independently in chimpanzees/bonobos vs. gorillas. He also makes a persuasive case that this adaptation is responsible for making it much harder for African apes to walk upright efficiently, because they are forced to twist their body with, rather than counter to, their hips. This, then, would explain the parallel adoption of knuckle-walking by the two lineages during or after their divergence from each other and also from that leading to humans, which appear to have happened in one event (with gorillas diverging earlier from a lineage that later split to create those leading to chimps/bonobos on the one hand and humans on the other, although IMO a more complex triple split with a sustained period of reduced gene flow is more consistent with the evidence). The common ancestor was either small, made little use of brachiation, or both. After the split, both lineages developed into comparatively large-bodied brachiators, later becoming increasingly terrestrial and now dependent on knuckle-walking where the common ancestor would have used upright walking somewhat similar to that of gibbons and siamangs.

A suggestion (by Thorpe, Holder, and Crompton) that bipedalism developed among arboreal apes as "an Adaptation for Locomotion on Flexible Branches"^[7] was countered by a comment (by Begun, Richmond, and Strait) referring to the evidence of shared features indicative of knuckle-walking and appealing to parsimony as demonstrating its use in the common ancestor of humans and African apes.^[9] With this paper,^[2] we see the argument of the Begun team dissolve: There is no longer any strong evidence of knuckle-walking in the common ancestor, or any of the central lineage(s) of the great apes.

The Thorpe/Crompton team hasn't stood still, a more recent review examines a great deal of detail regarding the mechanics of locomotion, especially with respect to foot-ground contact and the movement of the center of gravity (COG), in support of an arboreal origin for bipedalism. They deal with the knuckle-walking hypothesis thus:^[5]

To our knowledge, Gebo is the only supporter of the knuckle-walking hypothesis to have offered a functional argument linking knuckle-walking and the origins of modern human bipedality, but as we have shown, his argument, which is restricted to foot function, is poorly supported by the data. No explanation appears to have been offered of how the characteristic flexed hindlimb postures of knuckle-walking gait could have been pre-adaptive for the extended hindlimb postures of modern human walking, or indeed how the transformation could have occurred. Further, the knuckle-walking hypothesis requires that orthogrady evolved twice: from pronograde simians to the orthograde crown hominoids – and then following an adoption of terrestrial knuckle-walking by the common African ape ancestor to orthograde bipedality in hominins. We prefer the alternative, that knuckle-walking evolved evolved independently in gorillines and panins, as the ontogeny of phalangeal and metacarpal scaling ([ref]) and of other 'knuckle-walking features' ([ref]) is different in panins and gorillines, suggesting that knuckle-walking evolved more than once among the African apes.

Kivell and Schmitt have certainly provided great support for this preference. However, there are some problems with this latest (AFAIK) volley.

Although they mention Filler's work with homeotic mutations,^[4] Crompton et al. do not (as far as I can tell) take note of the implications of lumbar stiffening as an adaptation for brachiation in larger-bodied apes, although it seems fully consistent with their model. Apes that spent most of their time clambering around in an upright position (with little brachiation) might well have had no need for such lumbar stiffening. More importantly, Crompton et al. fail to allow for the selective advantage of the springy backbone supporting the upper body. (In fact, even Filler puts more emphasis on support standing or walking rather than running.)

Crompton et al. actually discuss the use of heel-strike in walking by various apes, and mention the "lack of heel-strike in modern hylobatids",^[5] but fail to make the connection to the shock-absorbing, and especially energy-storing capacity, of the springy lumbar structures of Great apes (including humans). Of course, I don't recall any special emphasis on this in the book, but then the Filler wasn't arguing against the Thorpe/Crompton suggestion of arboreal bipedalism. Although I can't speak as an expert, it seems to me that the advantages of the Great Ape lumbar structure would primarily apply to ground and very large branches/trunks, where the elastic support for the upper body could cushion the jarring effect of the heel-strike and store at least part of its energy. Landing on smaller branches with a heel-strike would be less problem, as they could provide the springy support, alternatively too much force could destabilize things, so the heel-strikes used by Great Apes on small branches are probably as careful as those of humans on icy pavement.

Problems with Current Selective Models

What this suggests to me is that the stem lineages of great apes relied much more on terrestrial movement than Crompton et al. suggest.^[5] Of course, reliance doesn't necessarily mean frequent use. One major problem I have with all these studies is their tacit assumption that energy efficiency, or frequent use, represent a good measure of selective advantage. Apes are social animals, which means that intra-specific competition is extrememly important in selection, both within and between social groups. The "winners" of these competitions could be expected to have as much as they needed to eat, so energy efficiency would be less important than victory. Similarly, all such competition is ultimately "life-and-death", at least reproductively, given the reproductive advantages accruing to high-status individuals, so adaptations that reduce the risk of high-risk behavior involved in such competition would likely be selectively advantageous even at the cost of efficiency, and even when the behavior involved is not frequent.

In arguing for an arboreal origin for bipedalism, Crompton et al. state:

Kingdon (2003) has proposed that in Africa, from the Middle to Late Miocene, fragmentation of closed forest alternated with reclosure and reinvasion of gallery-forest, moist-woodland and rainforest environments, changes also clearly documented by Elton (2008)^[13]. Within branches of both the Pan and the Gorilla lineages, the height-range and frequency of vertical climbing locomotion must have increased, suggests Kingdon (2003), to facilitate access to preferred foods in the main and emergent canopy, while permitting travel between trees in broken-canopy woodland on the ground. Middle Miocene crown hominoids, such as Hispanopithecus (Dryopithecus) laietanus, are of a similar size range to living great apes, although undoubtedly male body weights for living great apes exceed estimated values for the Miocene. Thorpe et al. (2007a)^[7] thus speculate that the gorillines and panins, independently, became increasingly specialized on forelimb power, to sustain safety and effectiveness of increased vertical climbing, and so tended to adopt similar, extended-elbow, flexed-hip-and-knee kinematics when moving on the ground, hindlimb musculature being unable readily to sustain hip and knee extension and hence a bipedal gait. Hominin ancestors, we speculate, sacrificed continued access to the canopy, and became increasingly ground and small-tree dwellers. Lacking the increased specializations for vertical climbing, they were able to sustain a bipedal gait – and we may add, inasmuch as they were terrestrial, that they could sacrifice coronal-plane mobility, which also characterizes the orangutan, in favour of more effective parasagittal force-production.

Alternatively, my best interpretation of Filler would suggest that the "gorillines and panins, independently, became increasingly specialized on" brachiation, perhaps not often but in selectively critical circumstances, producing the independent lengthening of the hip and stiffening of the lumbar region adduced by Filler, but making the ancestral bipedalism very inefficient, producing independent adaptations for knuckle-walking. "Hominin ancestors", pretty much retained the ancestral condition, which would be very Australopithecus-like. Only with the appearance of the lineage(s) called "Homo habilis" and the transition to a Homo erectus-like form do we find the more sophisticated gaits found in modern humans.

The suggestion that the ancestral "Great Apes" possessed a functional upright bipedalism pretty much identical to that of the Australopithecenes, with all the modern "Great Ape" lineages representing separate offshoots independently adapted for arboreal lifestyles at the expense of the ancestral bipedalism, is generally consistent with both Filler and the Thorpe/Crompton team. However, the issue of the relationship between heel-strike and the lumbar modifications speaks for a much greater reliance on terrestrial movement than is consistent with the Thorpe/Crompton arboreal explanations.

Although Filler didn't speak to it, I think we should consider the environmental implications: conditions were not always a closed canopy:

Mid and late Miocene African catarrhines are associated with a variety of habitats, over time as well as in different places ([refs]). Early Miocene sites such as Mfwangano Island and Songhor, sampling several catarrhine genera including Proconsul and Rangwapithecus, probably had environments containing evergreen, multi-canopied forest ([refs]). The early Miocene catarrhines radiated extensively into such arboreal habitats, filling frugivorous, folivorous, above-branch and mixed arboreal/terrestrial niches ([ref]). The slightly more recent (c. 18 Ma) Hiwegi Formation on Rusinga Island, by contrast, appears to have single-canopied, disturbed woodland, known best from a rich floral assemblage ([ref]). Unfortunately, it has no directly associated ape fossils although several taxa are known from Rusinga Island deposits of a similar age ([ref]).^[13]

Given the widespread lack of fossils, we can't assume that any area lacking fossils lacked some sort of ape population. Proconsul, according to Filler,^[3] did not possess the specialized lumbar structures found in Great Apes, although a very similar species did. The "evergreen, multi-canopied forest" mentioned by Elton^[13] may well have been similar to the primary environments of both African and Asian modern Great Apes, while the "single-canopied, disturbed woodland" is another type of environment entirely. With broken canopies, and even a single canopy which would not have been completely opaque, there would have been much more undergrowth. This in turn would have led to much more scrambling and clambering moving over the ground. The "disturbed" aspect of the woodland suggests considerable downwood, placing all sorts of obstacles to overland transport. I would suggest that from the earliest expansion of the "Great Apes", that is those possessing the lumbar adaptations adduced by Filler, they specialized in rapid movement through this sort of terrain.

Figure 2: Example of "disturbance": damages of storm Kyrill in Wittgenstein, Germany. (From Wiki.)

In areas with high relief (from erosion), there wouldn't have been a clear boundary between this sort of movement and low arboreal movement through the "single-canopied, disturbed woodland". Mammals the size of Proconsul spend a lot more energy in vertical movement than horizontal,^A1 so an ability to move horizontally, or as close to it as possible, through a variety of micro-landscapes would be adaptive. So would an ability to run (when necessary, see above) over hard ground and large branches/logs at similar levels. Unlike the "assisted bipedal walk"^[12] that may be the safest way to cross high bridges, bipedal running during necessary high-risk activity would probably have depended on balance. This is hardly surprising, many primates can be taught to ride a bicycle, a task demanding great balance.

Figure 3: High relief terrain, from Oregon. This is badlands, much less wooded than the type of terrain I'm discussing, but it allows you to see the relief because of the lack of vegetation. Imagine forest over this terrain, with frequent disturbance as in Figure 2. (From the files of OregonLive.com.)

Given the generally Australopithecus-like fossils being found in Africa, some evidently dating back as early, or earlier, than the best date for the split between the lineages leading to humans vs. chimps/bonobos,^{[5] [13]} even parsimony, unreliable as it is, would suggest that the common ancestor was pretty much Australopithecus-like.

We can extend this argument to orangutans: given the many apparent similarities shared by humans and orangutans but not by chimps or gorillas, these may well have been inherited from an Australopithecus-like ancestor. In this case the arboreal (brachiating) adaptations of all three lineages would have been evolved independently, with different suites of ancestral features retained to be shared with humans.

Personally, I find Filler's hypothesis very convincing, more so than either the Knuckle-walking or the arboreal bipedalism explanations. And this paper provides strong support (although it doesn't say anything against arboreal bipedalism).

Kivell, T., & Schmitt, D. (2009). Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0901280106

Appendix: You can use the back key to return to where you were, or click on the quoted text to return to the line with the footnote.

A1. "Mammals the size of Proconsul spend a lot more energy in vertical movement than horizontal": This is because the mammalian ratio of basal metabolic rate to weight decreases with weight differently than the energy involved in vertical movement varies with weight, as does the energy involved in movement at all. I have been unable to find any discussion of this online, and can't even recall where I read it. I find it hard to believe that this subject has been ignored in discussions of arborial vs. terrestrial movement: I suspect there's something wrong with my search technique.

Basically, an animal the size of a squirrel spends almost as much energy moving horizontally as vertically, and the difference isn't all that large (for mammals with their high metabolic rate) from standing still. Both differences increase with increasing body weight (technically, mass). Obviously, the effect also varies by type of movement.

Links: I've included only the links called out in this leader. Not all of these links are called out in the text. Use the back key if you came via clicking a footnote.

1. Bipedal Humans Came Down From The Trees, Not Up From The Ground ScienceDaily (Aug. 11, 2009) not peer reviewed

2. Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor paywall

3. The Upright Ape: A New Origin of the Species by Aaron G. Filler MD, PhD

4. Homeotic Evolution in the Mammalia: Diversification of Therian Axial Seriation and the Morphogenetic Basis of Human Origins open access

5. Locomotion and posture from the common hominoid ancestor to fully modern hominins, with special reference to the last common panin/hominin ancestor paywall

6. Orangutan positional behavior and the nature of arboreal locomotion in Hominoidea

7. Origin of human bipedalism as an adaptation for locomotion on flexible branches free registration required

8. The Origins of Human Bipedalism paywall

9. Comment on "Origin of Human Bipedalism As an Adaptation for Locomotion on Flexible Branches" Open Access

10. Response to Comment on "Origin of Human Bipedalism As an Adaptation for Locomotion on Flexible Branches" Open Access

11. Locomotor Ecology of Wild Orangutans (Pongo pygmaeus abelii) in the Gunung Leuser Ecosystem, Sumatra, Indonesia: A Multivariate Analysis Using Log-Linear Modelling paywall

12. Orangutan Positional Behavior and the Nature of Arboreal Locomotion in Hominoidea

13. The environmental context of human evolutionary history in Eurasia and Africa Open Access

In the Google Top 20

2009-08-12T12:07:00.000-05:00

While browsing through the detailed reports from Sitemeter, I just made gratifying discovery: one of my posts is currently in the top 20 for a major Google search: The Nature of the Neocortex shows up on page 2 (Results 11 - 20 of about 807,000 for neocortex) of the results page for a search on "Neocortex".

I don't know much about how Google orders its search results, although I've heard that number of links and traffic have something to do with it. And, although I shouldn't say it, perhaps the fact that they advertise on this site has something to do with it. But Google advertizes on a lot of sites, and I'm guessing they get a lot more clicks from sites with less of a focus on nit-picking scientific details.

I don't know how long it will stay on the top 20: perhaps semi-forever, perhaps it will be lower tomorrow. But thanks to all the readers who created and/or followed links to that post.

A New Integrative Theory for Cortical Pyramidal Neurons

2009-08-11T19:20:00.001-05:00

A discovery reported in last Friday's Science Magazine offers a new unifying principle for how pyramidal cells perform their function in the neocortex, as well as other cortical areas: Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle (by Matthew E. Larkum, Thomas Nevian, Maya Sandler, Alon Polsky, and Jackie Schiller), unfortunately behind a paywall. What this paper does is demonstrate that a type of neural activity called an NMDA spike (see below), already known to occur in the basal branches of the dendrites of pyramidal cells, also occur in the branches in the apical tuft, the arborization that occurs at the top of the apical dendrite, the main dendrite that reaches from the soma (body) up to the top layer (Layer I) where the majority of synaptic connections are made between incoming axons (from other brain regions) and pyramidal cells (which produce outgoing axons to other brain regions).^[1]

As of late 2007, "NMDA spikes have been observed in basal dendrites but not apical dendrites",^[4] but now:

We report the existence of N-methyl-D-aspartate (NMDA) spikes in the fine distal tuft dendrites that otherwise did not support the initiation of calcium spikes. Both direct measurements and computer simulations showed that NMDA spikes are the dominant mechanism by which distal synaptic input leads to firing of the neuron and provide the substrate for complex parallel processing of top-down input arriving at the tuft.^[1]

Before we look at what these NMDA spikes are, let's look briefly at the implications of this discovery:

Integrative Calculations in Pyramidal Neurons

Figure 1: Structures of selected pyramidal neurons from different cortical areas. Click here to see full image and original caption. (From Reference 4, figure 1..)

Figure 2: Simplified (!) diagram of the calculating modules according to the "New Unifying Principle" in Reference 1. Each box represents an integrative calculating unit, capable of performing a large variety of calculations with its inputs. The circles represent input information coming via synapses. Note that the logical organization here doesn't map exactly to the physical organization of the neuron: the non-linear voltage responses of the synapses, the locations of the synapses on the local branches, and the non-linear voltage responses of the dendritic membrane of the local branches should all be considered part of the calculation box. The input, then, consists of the flow of neurotransmitters across the synapse. The timing of the arrival of the action potential, and any calculations that take place in the pre-synaptic neuron, aren't included in this diagram. Click on image to see larger version. (Original. You may link to, copy, and/or modify this image, as long as you give credit with a link to this post.)

Looking at Figure 2, we can see that there are a number of modules, potentially nested, which perform semi-independent calculations. They feed their results to modules progressively closer (and ultimately identical) to the soma, which (along with the axon hillock and the first 50-100 microns of the axon) performs the final calculation regarding whether, and when, to fire an action potential. Prior to this research, the modules in the apical tuft (those feeding the proximate apical dendrite, see also figure 1) were regarded as different in kind from those in the basal branches.^[4] What this research has (tentatively) demonstrated is that the integrating modules called "Fine Dendrite Branches" in Figure 2 appear to act in very similar fashions, although they provide their outputs to different places.^[1]

The outputs of from the tuft branches feed the integrating/calculating module represented by the proximate apical dendrite, which performs a calculation that involves a process called a "calcium spike" (see below), which had been thought to be caused in the tuft branches,^[4] but with this research are (tentatively) shown not to be caused in the branches, but only in the proximate apical dendrite.^[1] This permits the "New Unifying Principle":

The thin distal tuft and basal dendrites of pyramidal neurons, which receive the overwhelming majority of synaptic inputs ([ref]), appear to constitute a class of dendrite in which NMDA spikes are the predominant regenerative events summing synaptic inputs in semi-independent compartments. The output of each subunit in this class of dendrite is passed on to the major sites of integration at the axon and apical calcium initiation zones, which can all interact via actively propagated signals ([ref]), enabling the interactions between top-down and bottom-up information.^[1]

This represents a major change to how pyramidal cells should be viewed, offering different pictures of their modular breakdown and evolution. ... We can reasonably suppose that the evolution of the neocortex involved, among other things, some improvements and refinements to the integrating calculation process of the apical calcium initiation zones in the proximate apical dendrite. Pyramidal neurons "are abundant in the cerebral cortex of virtually every mammal that has ever been studied, as well as in those of birds, fish and reptiles, but not amphibians."^[4] They are:

found in most mammalian forebrain structures, including the cerebral cortex, the hippocampus and the amygdala, but not the olfactory bulb, the striatum, the midbrain, the hindbrain or the spinal cord. Thus, they are found primarily in structures that are associated with advanced cognitive functions[.]^[4]

We can reasonably suppose that the original version, developed either by early amniotes (and independently by fish), or much earlier in vertebrate evolution (and lost by ancestral amphibians), was only capable of supporting the three-layer cortical structure of reptiles and the allocortex of mammals.

Currents, Spikes, and Action Potentials

The functioning of a neuron is very complex, with a very large number of interacting "moving parts". Any effort to simplify the picture to the point that it can be discussed in a blog post will inevitably lose critical details, as well as producing a picture that fails to apply to most types of these cells. Nevertheless, we can look at a few general processes that are common to most (if not all) neurons.

The first thing we need to consider is the cell membrane, and various differences between the inside and outside. The two critical differences for our purposes are the voltage across the membrane, and the different concentrations of certain critical ions: sodium (Na⁺), calcium (Ca⁺²), potassium (K⁺), and chloride (Cl^-). Both the concentration differences and the voltage tend to drive a movement of ions across the membrane, however they can't get through the membrane proper without the help of ion channels, of which every type of neuron is provided with a large number of many types. In a typical resting state, Na⁺ is being "pulled" into the cell by both concentration difference and voltage, while K⁺ is closer to equilibrium, with a smaller "push" outwards because the resting voltage across the membrane isn't quite enough to balance the difference in concentrations. Ca⁺² is being "pulled" inwards even harder than Na⁺, while Cl^- is a special case, in some neuron membranes at rest seeing a slight "pull" inwards, while in others there's a slight "push" outwards.^{[22] [23]} (I won't be covering Cl^- in this post, this is a subject for a future post.) Each ion has an equilibrium voltage which will exactly balance the concentration difference.^[24]

Figure 3: Equilibrium Voltages and the Effect of Various Ion Currents on Membrane Potential. Note that the equilibrium voltages (E_Na⁺, E_Ca²⁺, E_K⁺, and E_Cl^-) are actually ranges, depending on the specific ion concentrations inside and out. This is especially important in the case of Cl^-, where variations in concentration can move the equilibrium voltage to either side of the Resting Membrane Potential. (Based on Reference 24 Figure 2.2, p41. You may link to, copy, and/or modify this image.)

Now, the actual voltage across the cell membrane will be determined by the relative concentrations of all (charged) ions, along with more transient effects created by various currents. These currents are caused by the flow of charged ions through ion channels and ion pumps. Ion pumps tend to run at a (roughly) constant rate, so their currents are roughly constant, balanced by typically small currents through ion channels that are slightly open at the resting voltage. This balance creates the resting voltage, and can be changed by long-term changes to ion channels that occur e.g. between various states of consciousness.^[24]

It's very important to realize that the membrane voltage, and concentration differences across the membrane with their associated equilibrium voltages, can vary between cells, between different parts of the cell, and over time even for the same part of the cell. A large number of factors go into determining the voltage, and even the concentration differences are subject to a number of interacting controls, not all of them part of the specific cell in question.^{[14] [24]}

Currents, both resting and transitory, are produced and controlled by a large number of ion channels, many of which have very complex and often time-dependent reactions to voltage, ion concentrations (including those that they don't pass, for instance there are two K⁺ currents, well enough known to be named, that are controlled by the internal Ca⁺² concentration: I_C and I_AHP, produced and controlled by calcium activated ion channels), and the concentrations of a large variety of messenger molecules and neurotransmitters, both inside and outside the cell.^[24]

A spike is a sudden change in voltage caused by a large transitory current of some sort. The best-known spike is the action potential, which is a regenerative positive-feedback current of sodium and/or calcium produced by voltage-gated channels for these ions. We need to consider what the word "regenerative" means in this context: when the voltage across the membrane drops to and past zero at one point on the membrane, it causes the voltage nearby also to drop, which in turn activates voltage-gated channels in these nearby positions, causing the positive feedback process that creates the action potential. (The voltage-gated channels usually shut after a short time (around a millisecond (ms)), especially the sodium channels that mediate the action potential in the axon, the best known.) This is the "regeneration": one process causes the voltage to drop at a specific point on the membrane, and when it passes a threshold a new, voltage-dependent process regenerates a further voltage drop, amplifying the initial impulse.

There are other types of spikes: localized non-propagating Na⁺ and Ca²⁺ regenerative currents that amplify local voltage changes caused by other currents. Sodium and Calcium are the principle spiking ions, because of the strong forces pulling them into the cell. In principle, K⁺ could also cause a spike, with the voltage change going in the other direction, but this doesn't seem to happen in nature. However, there are many types of spikes where channels open for both Na⁺ and K⁺, going in opposite directions and creating currents opposed to each other, where the much larger driving force on Na⁺ overwhelms the K⁺ force, producing a net inwards current.

We need, now, to take a closer look at the voltages involved. As you can see from figure 3, membrane voltage at any point can be moved by changes to any of the various currents. When a burst of neurotransmitters from an action potential arrives at a synapse, they will have various effects on the ion channels that are present, causing various currents. The effect of the currents is to either depolarize or hyperpolarize the membrane, bringing its voltage closer or farther away from the action potential threshold.^[24]

Figure 4: Action Potential Threshold and Directions of Depolarization and Hyperpolarization Relative to Figure 3. (Based on Reference 24 Figure 2.2, p41. You may link to, copy, and/or modify this image.)

Now, in an action potential, voltage-gated Na⁺ and/or Ca²⁺ channels open when the voltage falls below their threshold, causing a spike where the voltage continues to fall. Because there is a large number of such channels present throughout the local membrane, the spike at one point drags down the voltage at nearby points, causing the channels there to open. Thus the spike propagates itself at nearby points on the membrane, and moves away from its initiation point along the axon or back from the soma along the major dendrites, if they possess the right mix of voltage-gated channels.

Suppose, however, that there's just a large concentration of a certain type of voltage-gated channel at one point. In this case, the current created by ion channels responding to a burst of neurotransmitters (from an action potential in another neuron) might bring the voltage to the threshold, causing the concentration of channels to open and amplify the original current with a regenerative current of their own.

There is a constant rain of these bursts of neurotransmitters on various synapses at various locations on the dendritic arbor. Each creates currents, some depolarizing, some hyperpolarizing, and the effects spread from the synapse along the cell membrane. The original current fades as the neurotransmitters are taken up and their effects pass, meanwhile the voltage at the synapse decays as the charges transferred spread out along the membrane. Other synapses also see a voltage bump, with size and timing depending on their distance along the dendrite from the location of the arriving neurotransmitter burst, as well as the conduction qualities of the intervening membrane.^[24]

If an exitory (depolarizing) action potential arrives at a second (nearby) synapse while it is already somewhat depolarized from the earlier exitory action potential at the first, the current caused by the burst will start at a lower (more depolarized) voltage and thus drag the voltage at that point lower than it would if the membrane was at normal resting potential. If this lower voltage crosses the threshold for some concentration of a certain type of voltage-gated channels, they will open, creating a spike that wouldn't have happened in response to either action potential by itself.

In the dendrites, calcium spikes seem to be more common than sodium, although given its higher driving force channels that allow both through will probably show a bigger calcium effect than sodium.^[4] Calcium is useful in the dendrites, because the recovery from these spikes requires considerable energy and the elevated Ca⁺² levels inside the cell stimulate the mitochondria to start producing more energy immediately, rather than waiting for the energy use to draw down the ATP/ADP ratio (as I've discussed previously).

The effects of all these various currents, as spread while decaying to the soma, axon hillock, and first part of the axon, determines whether and when an action potential will fire. In order for that to happen, the voltage at the critical point (depending on the cell type) must fall below the threshold as a result of the combination of the effects of the various exitory (depolarizing) and inhibitory (hyperpolarizing) currents at various synapses.^[24] Large spikes in the dendrites can have a disproportionately large effect here, touching off action potentials when the combination of the original currents would never have caused this.^[1]

Types of Spikes in Pyramidal Cell Dendrites

There are two major types of spikes that participate in dendritic calculation: calcium spikes and NMDA spikes.^[1] Calcium spikes often propagate in a regenerative process similar to the action potential, at least in the apical dendrite (see Figure 1).^[4] They carry information generated in the apical tuft to the soma, where they can participate in the final decision whether/when to fire an action potential. They are similar to sodium-driven action potentials, in that when a certain threshold depolarization is reached voltage-driven calcium channels open, causing a positive feedback.^[4] The typical recovery is mediated by calcium activated K⁺ channels which tend to be somewhat slower than those involved in the Na⁺-based action potential seen in the axon. Once these channels open, the K⁺ current tends to repolarize and hyperpolarize the local membrane before they close, because unlike the voltage-gated K⁺ channels involved in the classic action potential they don't respond to changes in voltage, but stay open until the uptake of Ca²⁺ by the mitochondria is complete.^[24]

NMDA spikes are different.^[12] NMDA receptors are for glutamate, the most common exitory neurotransmitter in the brain. It is not the only one, the major fast response to glutamate from an action potential is mediated by AMPA receptors. AMPA receptors are pretty much voltage independent: they translate a certain sized burst of glutamate into a specific current of sodium and perhaps calcium (depending on the type). NMDA receptors, OTOH, are both voltage sensitive and in need of some quantities of glycine, an otherwise inhibitory neurotransmitter released by other types of cells in the brain. NMDA receptors are also subject to modulation by a wide variety of different substances, which can modify their response to glutamate as well as the threshold voltage for opening.

This threshold is caused by the tendency of extracellular Mg²⁺ to block the pore through which ions travel at higher (more polarized) voltages. Thus a burst of glutamate can arrive at a synapse and cause only a small (or non-existent) current from AMPA receptors, while a much larger number of NMDA receptors stay silent, or perhaps only join in when the voltage is at its peak of depolarization. However, if the synapse is already depolarized somewhat from other effects, including currents from action potentials at other synapses, nearby spikes (calcium and NMDA), and back-propagating action potentials form the soma, the arrival of the burst of glutamate could instead cause a much larger current: an NMDA spike.^[12] (We should note that NMDA receptors are pretty non-specific regarding which positive ions they will pass: Na⁺, K⁺, and Ca²⁺ will all have currents.)

These spikes tend to support very localized calculations.^[1] Inhibitory synapses, using either GABA or glycine, tend to produce Cl^- currents, which in the dendrites are usually hyperpolarizing and also tend to resist the depolarizing effect of other exitory effects in their immediate vicinity. These synapses, then, have a much greater effect in suppressing NMDA spikes in nearby exitory (depolarizing) synapses than their effect on the final voltage as felt at the soma. The localized interactions tend to convert the fine dendritic branches of the basal dendrites into semi-independent calculating modules, and the implication of the paper being covered here is that the same is true of the fine dendritic branches of the apical tuft. Thus, the exact same mechanism is used in both types of calculating module.^[1] We should also note that the ability of so many substances to modulate the threshold voltage of the NMDA receptor means that chemically mediated information is input directly into the most basic and fundamental system of dendritic calculation in the neocortex, as well as the rest of the "cerebral cortex, the hippocampus and the amygdala [...] primarily in structures that are associated with advanced cognitive functions".^[4] We should also note that these local calculations aren't limited to the dendrites of the cell ultimately firing the action potential: the immediate chemical environment of both the NMDA receptors in the synapse and the various voltage-gated channels in the local membrane between them is subject to influences with sub-second timing from local membranes of many other nearby cells, both neurons and glia, as I've discussed before.

Contra the previous understanding, calcium spikes in the studied pyramidal neurons appear to be limited to the proximate apical dendrite (see Figures 1&2),^[1] where "[s]everal properties, including the existence of local NMDA spikes and the weak electrogenesis of both sodium and calcium spikes, suggest that the relationship of the fine distal tuft branches to the apical Ca²⁺ initiation zone is similar to the relationship of the basal dendrites to the axosomatic initiation zone".^[1] In Figure 2, then, we can see that the proximate apical dendrite serves as a "smart" relay, integrating the calculations made in the distal branches of the apical tuft and passing along the result to the soma (and axon hillock and early axon) where it is integrated with the results of calculations made (using the same or similar process) in the distal branches of the basal dendrites.

While there appear to be some minor differences between the apical and basal mechanisms, such as the "presence of hyperpolarization-activated current (I_h)" in apical dendrites,^[1] these can probably be regarded as "fine-tuning" of the working of the integration process, perhaps to adapt it to the different functions of the apical and basal dendrites. Overall, the similarity of function presented in this paper supports a much more unified paradigm for how calculations in pyramidal cells actually work.

Larkum, M., Nevian, T., Sandler, M., Polsky, A., & Schiller, J. (2009). Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle Science, 325 (5941), 756-760 DOI: 10.1126/science.1171958

Links: I've included only the links called out in this leader.Only a few of the links here are called out in the text. Far too many are behind paywalls; I've mentioned where links are formally open access. Use the back key if you came by clicking a footnote.

1. Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle paywall

2. In vivo two-photon voltage-sensitive dye imaging reveals top-down control of cortical layers 1 and 2 during wakefulness

3. Thalamic Input to Distal Apical Dendrites in Neocortical Layer 1 Is Massive and Highly Convergent paywall

4. Pyramidal neurons: dendritic structure and synaptic integration

5. Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study

6. Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials Open Access

7. Computational subunits in thin dendrites of pyramidal cells

8. Ca²⁺ accumulations in dendrites of neocortical pyramidal neurons: An apical band and evidence for two functional compartments paywall

9. Signaling of Layer 1 and Whisker-Evoked Ca2+ and Na+ Action Potentials in Distal and Terminal Dendrites of Rat Neocortical Pyramidal Neurons In Vitro and In Vivo Open Access

10. Apical tuft input efficacy in layer 5 pyramidal cells from rat visual cortex Open Access

11. Role of dendritic synapse location in the control of action potential output

12. The Properties and Implications of NMDA Spikes in Neocortical Pyramidal Cells Open Access

13. Spatiotemporally Graded NMDA Spike/Plateau Potentials in Basal Dendrites of Neocortical Pyramidal Neurons Open Access

14. Astrocytic control of synaptic NMDA receptors Open Access

15. NMDA receptor-mediated dendritic spikes and coincident signal amplification paywall

16. Diversity and Dynamics of Dendritic Signaling

17. Dendritic arithmetic

18. Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites

19. Dendritic Computation

20. Integrative Properties of Radial Oblique Dendrites in Hippocampal CA1 Pyramidal Neurons Open Access

21. Dendrites: bug or feature?

22. Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits requires free registration

23. Cation–chloride co-transporters in neuronal communication, development and trauma paywall

24. The synaptic organization of the brain Edited by Gordon M. Shepherd

Scientia Pro Publica 9 is Up

2009-08-03T17:16:00.000-05:00

Here.

Obviously, I'm not skipping a big post today: after over two weeks without one, this morning's began to break the logjam. Unfortunately, there's more to writing my posts than reading the appropriate papers and writing the post: there's integrating and "making sense of" the mass of facts so they fit into a comprehensible framework. The process tends to "clump", so there'll be dry periods, and weeks like the one that ended with Nature of the Neocortex, with four big posts.

This is relevant because today's "Pro Publica" features my surprisingly successful Nature of the Neocortex, which I'm still trying to work out how/why (of the success). It built on many previous posts, integrating ideas that would have been clumsy if I'd had to introduce them cold. That may explain its popularity with regular readers, but not the number of new, outside links with recommendations. I suppose my efforts to avoid jargon (and explain what I couldn't avoid) might be part of it, and I certainly hope my efforts to rationalize the details in both developmental and evolutionary terms contributed.

Back to Scientia Pro Publica 9, it's got a lot of good stuff in it, and I recommend giving it a good lookover.

Carnival of Evolution 14 is Up

2009-08-03T13:46:00.000-05:00

(Actually last Saturday, but I missed it until now.)

Here.

Neocortex, Allocortex, and Nuclei, and the Remapping of Their Connections

2009-08-03T11:37:00.001-05:00

The mammalian brain is made up of many parts, each pretty much unique. However, these various parts, or at least the "gray matter" of them, can be roughly grouped into three classes of structure, or even more roughly into two: nucleus and cortex. The word "cortex" comes from the Latin, meaning "bark", "rind", "shell" or "husk". In the case of gray matter, it usually denotes a relatively thin layer of gray matter covering thicker white: such as the neocortex, the piriform cortex, or many other cortical areas in mammals and other vertebrates. In a recent post, I described the neocortex, comparing and contrasting it with other forms, which are loosely grouped together as "allocortex". (Meaning "other cortex" with a connotation for "other" of "like but not identical". This from the Greek prefix "allo-" which we may contrast with the alternative prefix "hetero-" which means "unlike".)

The class of structure I haven't touched on yet is the nucleus: defined by Wiki as "a brain structure consisting of a relatively compact cluster of neurons." Quoting further:

The term "nucleus" is in some cases used rather loosely, to mean simply an identifiably distinct group of neurons, even if they are spread over an extended area. The reticular nucleus of the thalamus, for example, is a thin layer of inhibitory neurons that surrounds the thalamus.

In this respect, the word parallels "allocortex", which also covers a variety of forms. Only the Neocortex has a very precise description, and even here only by excluding the parts of the hippocampus in which neurons mature from the outside in as they do in the neocortex. In addition, the cortical structure of the Cerebellum should probably be given its own term, considering the very old and very sophisticated developmental mechanisms unique to it. I'm not going to discuss the Cerebellum in this post, it deserves its own, along with more detailed research than I've done to date on its evolution.

In several posts, I've discussed the general nature of the "gray matter", focusing on "neuropil", which is generally defined as a tangled mass of neurites, glial and sometimes neural somas, and glial extensions (which would be called neurites if they were possessed by neurons rather than glia). The neuropil is where the real work of calculation takes place, since is contains most of the active dendritic arbor (one way or another) as well as most of the synapses and a goodly part of the axonic arbor. The relationship between the mass of neural somas and the neuropil varies by region of the brain, being different in at least some details for just about each region studied.

In many parts of the brain and Central Nervous System (CNS) a set of similar structures call glomeruli turn up. These have been extensively studied and described in the olfactory system, where they are part of the olfactory bulb, which forms a "way station" of sorts between the olfactory epithelium which contains the actual sensory cells, and the deeper parts of the brain, including the piriform cortex and the amygdala and hypothalamus.

Glomeruli have also been studied in the cerebellum (Wiki only describes them in these two spots, as well as superficially similar structures in the kidney), but studies have been made of similar structures in many places in the CNS, including, for instance, the trigeminal nucleus.^[1] In general, a glomerulus can be described as a tangle of neuropil surrounded by a tighter structure of neural and glial somas cells with extensions of both into the central part. In many (perhaps most) types of glomeruli, diffusion of neurohormones through the central part is easy and fast enough that most of the neurites inhabit the same extracellular concentrations of signaling molecules, at least on a time-scale of seconds or more. The tight structure of the surrounding cell bodies, along with (presumably) greater uptake rates by glial cell membranes, would tend to isolate the concentrations within any one glomerulus from even its nearest neighbors. In contrast to the typical neuropil of the neocortex, where concentrations of emitted extra-synaptic neurohormones might vary over micron scales or less, it seems likely that the extra-synaptic concentrations of glomeruli are pretty much normalized.

All of these brain structures depend on the axon bundles (called "tracts" in the brain, although they are called "nerves" in the periphery, per Wiki) to transmit information between the more detailed calculations in the neuropil. ... Indeed, in the more traditional view, the primary calculation was simply whether/when to fire an action potential, which was regarded as the key to the brain's activity. Recent research has thoroughly undercut this view, as I've discussed in several posts. However, even with this new information, the "wiring" of axonal connections is critical to the working of the brain.

Which brings us to a very important research paper,^[13] published in last Friday's Science Magazine: Pre-Target Axon Sorting Establishes the Neural Map Topography (by Takeshi Imai, Takahiro Yamazaki, Reiko Kobayakawa, Ko Kobayakawa, Takaya Abe, Misao Suzuki, and Hitoshi Sakano). This paper is, unfortunately, behind a paywall, but I'm going to describe the finding in general terms, then go on to its importance, especially in terms of how we can generalize from the olfactory system to the brain in general.

We need to start with a brief description of how the olfactory sense in mammals works: it begins with the olfactory epithelium, which is a structure inside the nose, where mucus with absorbed volatiles comes in contact with olfactory sensory neurons (OSNs). (There is a organ called the vomeronasal organ which is the input to the accessory olfactory system which I'm not going to discuss here.) Each OSN expresses one specific odorant receptor (OR), of which there are around a thousand in mice, rabbits, and other mammals that have retained the ancestral focus on this sense. (Humans have about 350.^[23]) Actually, this is the number of genes, there are two copies, one from each parent, and any specific cell only expresses one of those copies.^[13]

The distribution of OSNs expressing any one OR within the olfactory epithelium tends to be quite specific, pretty much identical from one member of a species to another. Although the surface of the olfactory epithelium is rather convoluted, it can be unfolded into a roughly planar surface, extending from dorsomedial (upper/inner) to ventrolateral (lower/outer) in one dimension, and anterior to posterior (front to back) in the other. The OSNs expressing a specific OR will all lie in a rather narrow stripe extending all the way from anterior to posterior, but only a small part of the dorsomedial to ventrolateral dimension.^[13]

Now, as mentioned above, the olfactory bulb serves as a "way station" between the olfactory epithelium and the deeper (higher) regions of the brain. What happens is that there's one glomerulus (on each side) in the olfactory bulb for each specific OR, and axons from all the OSN's expressing that OR end up at that glomerulus. The surface of the olfactory bulb, like the olfactory epithelium, can be mapped as a rough plane, and the dorsal-ventral axis seems to map clearly to the dorsomedial-ventrolateral axis of the olfactory epithelium. So any glomerulus will show up at a location on the dorsal/ventral axis of the olfactory bulb that corresponds to the location of the stripe on the olfactory epithelium. (Actually, there are two sections to the olfactory bulb, the "Main olfactory bulb" and the "Accessory olfactory bulb", part of the accessory olfactory system, but this is not really critical to the discussion at hand and will be left out.)

But it's much more complex along the other axis. There are many different OSN's occupying the same stripe of the olfactory epithelium, and there will be many glomeruli occupying a similar (mapped) stripe within the olfactory bulb. How do the neurons sort themselvs out so that all of those expressing one OR end up at the same glomerulus? What Imai, Yamazaki, et al. have demonstrated is that the axons actually sort themselves into their proper order while growing from the epithelium towards the bulb.

They do this using varying gradients of expression of Neuropilin-1, a multi-purpose receptor for several agonists, including "the secreted repulsive ligand Semaphorin-3A (Sema3A)." This ligand is "expressed not only in the target, but also in OSNs. Single-cell microarray analysis revealed that Nrp1 and Sema3A genes are regulated in a complementary manner by OR-derived cAMP signals".^[13] That means that the more the ligand is expressed, the less the receptor is, and vice versa. By appropriate responses of the growing axons, the axons can sort themselves into the proper order before ever reaching their target in the olfactory bulb (OB)^[19]:

We found that pre-target axon sorting plays an important role in the organization of the topographic map. Nrp1 and its repulsive ligand Sema3A are both expressed in OSNs and are involved in axon sorting before targeting on the OB. Within the axon bundles of D-zone OSNs, DII-A axons (Nrp1 low, Sema3A high) are sorted to the central compartment of the bundle, whereas DII-P axons (Nrp1 high, Sema3A low) are sorted to the lateral-peripheral compartment. This sorting appears to occur, at least in part, by the repulsive interaction between Sema3A and Nrp1. In addition to the repulsive interactions, Sema3A and Nrp1 signals may induce homophilic adhesion of axons with Nrp1 itself ([ref]) or with other molecules such as L1 ([ref]). Furthermore, additional guidance receptors such as Plexin-A1 ([ref]) may be involved in the sorting of DII-A and DII-P axons (fig. S7). We assume that similar mechanisms are also at work in the sorting of DI and DII axons (Fig. 1B).

Once OSN axons are sorted in the bundle, they need to be oriented along the correct axis before projecting onto a topographic map on the OB. This probably requires positional cues that are derived from the target or that are found along the pathway between the olfactory epithelium and the OB. In the Sema3A total knockout, Nrp1-positive DII-P axons spread rather uniformly across diameter of the bundle (Fig. 5B) and consequently mistarget to the anterior region in the OB ([refs]). The effect is different in the OSN-specific Sema3A knockout, where DII-P axons at least gravitate toward the lateral region in the bundle (Fig. 5B). Thus, Sema3A expressed by cells outside of the bundle likely functions as an additional guidance cue to orient the sorted axons along the correct axis for projection onto OB. In early embryos, but not in postnatal mice, Sema3A is expressed in the anterior OB (Fig. 5A). Furthermore, Sema3A is found in ensheathing glial cells along the medial side of the axon bundles (Fig. 5A) ([ref]). Involvement of such intermediate cues has been reported for the thalamocortical projection ([refs]).^[13]

What this means is that the growing axons use varying expressions of the same ligands and receptors as their targets to orient and sort themselves into a rough approximation of the distribution of their targets, before the axon bundle ever reaches that target. In addition, there is evidence that similar varying expression (or at least secretion) of the ligands involved is provided by supporting glial cells. (Both neurons and glial cells have the ability to localize their secretion of various signaling molecules, as discussed in Nerve Cells and Glial Cells: Redefining the Foundation of Intelligence)

The implications are important. In a recent review: Development of Continuous and Discrete Neural Maps (by Liqun Luo1 and John G. Flanagan), which is open access, the differences between discrete neural maps such as found in the olfactory system, and continuous neural maps such as found in the retina and early visual areas of the brain, are discussed in detail. "Since visual retinotopic and olfactory glomerular maps represent two ends of a continuum that includes many other types of neural map in between, these emerging general principles may be widely applicable to map formation throughout the nervous system."^[11] The mechanisms used are very similar, although the precise means by which each OR maps to a specific concentration ratio of ligands and receptors appears to require more research. (My guess would be that the ORs actually release varying levels of cyclic Adenosine MonoPhosphate (cAMP) a signaling molecule used within the cell for a wide variety of purposes. Their levels of release in guiding axon growth are probably (IMO) independent of the level of release found when operating as olfactory receptors, presumably a different mode of stimulation is used during developmental nerve growth.)

What these facts demonstrate is that the axon tracts linking any two parts of the brain, can rearrange themselves from the source mapping to the target mapping. In the case of the olfactory epithelium, the "mapping" on the anterior/posterior axis appears to be random,^[13] for other systems, where it isn't actually random, such mapping can be treated as though it was.

Technically, only one of the two dimensions involved here is remapped, with the dorsomedial-ventrolateral axis of the olfactory epithelium mapping directly (ie without the need for remapping) to the dorsal/ventral axis of the olfactory bulb. So we can't use this as actual proof that brain regions can remap more than one dimension. However, if a mechanism like this can be developed once, it can be developed more times, and it's completely plausible that several dimensions of an n-dimensional space could be remapped between communicating brain regions. This is especially important in the neocortex, where the kind of complex and abstract n-dimensional transformations these functions support could be critical to making intelligence as we know it work.

I've discussed these ideas in Concepts, Cognition, and Anthropomorphism; this remapping process represents a critical enabling function for this kind of operation. The fact that it shows up in the olfactory system, arguably older than the neocortex, suggests that the development of this capability, or at least certain critical refinements of it, may have been a sine qua non for the development of the neocortex. Of course, until research into the presence (or absence) of such remapping is done in lizards, turtles, and amphibians, we can't actually know that the entire mechanism wasn't inherited from an earlier ancestor. Indeed, it may have been present in the earliest jawed fishes. Still, the appearance and expansion of the neocortex is significant, and until the needed research has been done, it might be best to tentatively assume that some improvements in neural remapping took place just prior to the development of the neocortex.

As for the nuclei, it may well be that these structures are primitive, in the sense that they don't require such remapping, or at least didn't in early vertebrates. Perhaps the default structure for early nuclei was for each incoming axon to arborize over the entire nucleus, picking and choosing its target cells entirely on the basis of local interactions. But once the remapping capability had been developed, it seems very likely it would have been reused for tracts targeting those nuclei where it would have been useful. Thus, we can't assume that nuclei in the mammalian brain don't involve such remapping processes.

Imai, T., Yamazaki, T., Kobayakawa, R., Kobayakawa, K., Abe, T., Suzuki, M., & Sakano, H. (2009). Pre-Target Axon Sorting Establishes the Neural Map Topography Science, 325 (5940), 585-590 DOI: 10.1126/science.1173596

Links: Only a few of these are actually called out in the text. I've only included the link called out in this leader. Use the "back" key if you came by clicking a footnote.

1. Synaptic organization of the substantia gelatinosa glomeruli in the spinal trigeminal nucleus of the adult cat paywall

2. From Pheromones to Behavior paywall

3. Evolutionary Convergence of Higher Brain Centers Spanning the Protostome-Deuterostome Boundary paywall

4. Lungfish evolution and development paywall

5. Forebrain evolution in bony fishes paywall

6. Dendritic neurotransmitter release and its modulation in accessory olfactory bulb circuits

7. Localization and Targeting of Voltage-Gated Ion Channels in Mammalian Central Neurons

8. Primary innervation of the avian and mammalian cochlear nucleus

9. Origin and function of olfactory bulb interneuron diversity paywall

10. Distribution and phenotypes of unipolar brush cells in relation to the granule cell system of the rat cochlear nucleus

11. Development of Continuous and Discrete Neural Maps

12. Contributions of Theoretical Modeling to the Understanding of Neural Map Development

13. Pre-Target Axon Sorting Establishes the Neural Map Topography paywall

14. Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb

15. Odorant Receptor–Derived cAMP Signals Direct Axonal Targeting free registration required

16. Roles of odorant receptors in projecting axons in the mouse olfactory system paywall

17. Tenascin-C Is an Inhibitory Boundary Molecule in the Developing Olfactory Bulb paywall

18. Axons find their way in the snow paywall

19. Odorant receptors at the growth cone are coupled to localized cAMP and Ca2+ increases

20. Neural map specification by gradients paywall

21. Innate versus learned odour processing in the mouse olfactory bulb paywall

22. Odor maps in the olfactory cortex

23. Neurobiology: Odorant receptors make scents paywall

24. Brain Maps.org

25. Cholinergic Modulation of Dopaminergic Neurons in the Mouse Olfactory Bulb

Scientia Pro Publica #8 Is Up...

2009-07-20T09:25:00.000-05:00

Here.

In honor of that, and because after last week's four big posts, I'm going to spend today on research (for future posts), there won't be a big one today.

A question for my readers: Saturday's post got a lot more positive response than any previous, and it was also more pointed towards explaining current understanding than my usual Kuhnian revolutionary efforts. Of course, I always try to provide an explanation of what I'm talking about, but that one was the first that really just pointed at summarizing current research, rather than focusing on places where, IMO, current research has gone astray (with, always, the exception(s) of the paper(s) I'm reviewing). Is this what readers want? Or rather, do you (readers) prefer posts that simply summarize current knowledge rather than pointing out major opportunities for paradigm-breaking research?

I promise to read and consider all your comments.

AK

The Nature of the Neocortex

2009-07-18T16:21:00.000-05:00

The neocortex is a mammalian invention, not present in birds, reptiles, or any other vertebrates. It's associated with the increases in intelligence seen in mammals since the end of the Cretaceous, especially in primates, and more especially in humans. While there are dozens (probably hundreds) of discussions of the neocortex available on the Web, I haven't been able to find one that meets my needs (for linking to in detailed discussions), so I'm going to produce my own, in the process discussing a recent paper which reflects on it.

The neocortex develops from a part of the developing neural tube called the telencephalic pallium.^[17] This is the part of the telencephalon that is towards the back (dorsal) and upper side (dorso-lateral), while the part towards the middle of the body (medial) develops into the hippocampus, including the dentate gyrus and some other parts of the brain associated with memory (especially spacial memory) and navigation. The bottom (ventral) part of the telencephalon develops into the basal nuclei, which "are associated with a variety of functions: motor control, cognition, emotions, and learning. [Wiki]" (The telencephalon is split into two parts, one on each side, a feature not visible in Figure 1.)

Figure 1: Parts of the neural tube. (From Wiki)

We'll come back to the neural tube, but for the moment let's take a look at the structure of the neocortex, by comparison with other structures: ... those that develop from the medial and ventro-lateral part of the pallium, and those in reptiles such as turtles and lizards (crocodilians are too closely related to dinosaurs and birds, and will not be considered) that have been shown to be almost certainly homologous to the neocortex: the dorsal and dorso-lateral cortex. These latter structures develop from the same part of the pallium in these reptiles as the neocortex does in mammals, and they share many similar connections, so it's worthwhile drawing parallels.

Most sites discussing the neocortex will tell you that it has six layers rather than the three found in these other structures, and that the cells mature from the outside in rather than the opposite. Many will also tell you that incoming axons arrive from the bottom rather than the top: that is from the direction of the inside of the neural tube rather than the outside. All these facts are generally true, although some details are often left out and the language is often obscured by the use of various anatomical terms. Let's go over it in detail.

The first difference has to do with the direction of maturity, the fact that cells mature from the outside in. Neurons in this part of the neural tube are created by cell divisions in the very inner part of the neural tube, called the ventricular zone.^[8] From there, they migrate radially, towards the outer part of the tube (called the pial surface). In turtles and lizards, these cells begin by settling in the outer part of what will become the dorsal cortex, and later cells settle inwards of them, closer to the center of the nerual tube. This is what is meant by outside-in maturation, since once they settle, these cells begin to mature.

What most sites discussing the neocortex don't mention is that in the mammalian hippocampus (except for the dentate gyrus) the first cells settle on the inside, closest to the middle of the neural tube, and later cells settle farther out.^[8] This is exactly what they do in the developing neocortex,^[25] which means that this change is not limited to the neocortex, but is somewhat more general to the mammalian pallium. It's a good guess that it came first, and it allows for a greater thickness of cortex with interconnections, even without the other changes, as is shown by the structure of the hippocampus.

The next change is the six-layered structure, which arises in the upper dorsal pallium and the dorsal part of the lateral pallium. This structure probably derives from the more primitive three-layered structure found in turtles, lizards, and the mammalian hippocampus, although the latter has evolved a much thicker outer layer and a characteristic "double-C pattern" with the dentate gyrus curved around the hippocampal gyrus. The three-layered structure in general is called the "allocortex": this word specifically stands for the parts of the "cerebral cortex" with a three-layered structure, although it's often used for other areas with the same cortical structure. (The "cerebral cortex" technically refers to the entire cortical area formed from the pallium, but is often instead mistakenly identified with the neocortex.)

We need to start by describing the three-layered structure, then, before we can compare it with the six-layered. The three layers are like a sandwich, with areas of mostly neurites (axons, dendrites, synapses, and glial cells) making up the bread, while the filling is densely filled with neural cell bodies (somas). Most of the neural connections come from the outside (the side away from the center of the primitive neural tube), while in this area most of the axons leaving do so out the bottom (the side towards the center of the neural tube). This provides for a simple "pass-through" system, in which the nerve cells process the incoming information and produce an output which goes to another brain region.

The disadvantage of this system is that the incoming axons are growing along the top of this layer, and trying to make synaptic connections with any cells they encounter.^[8] Since most of these cells don't want any specific connection, most of these attempts are refused, which constitutes a major waste of resources. Which leads us to the third difference, which is that many incoming axons from other parts of the brain come from below in mammals, in more evolved mammals, such as primates and carnivores, virtually all. We'll discuss this shortly.

Before we do so, we need to consider the layers of the neocortex, which are very different from the allocortex. The layers of the neocortex are usually numbered I through VI (usually using Roman numerals, although many websites use Arabic). Layer I is almost completely free of neuron somas, being mostly made up of neuropil, along with blood vessels and other support structures. Layers II and III have many neuron somas, a good mix of pyramidal cells (see below) and interneurons, the latter usually making local connections with their axons as well as their dendrites. Layer IV is composed of a mix of stellate cells, which like interneurons make local connections, in the sense that they typically don't extend their axons out of the area they reside, but they extend much farther than interneurons, and they tend to be exitory rather than inhibitory (see below). Layers V and VI contain mostly pyramidal cells, although with some interneurons, and the lower part of layer VI often contains a large proportion of neurites, especially axon branches.

In the allocortex, the majority of the interconnections are in the upper layer, although the lower layer (the one closest to the middle of the neural tube) has lateral extensions of outgoing axons, which make some connections, probably rising into or through the middle layer. In the neocortex, the bottom layer, called layer VI, roughly corresponds to this layer, consisting mostly of lateral branches of outgoing axons, which then make connections with other neurons (or glial cells). The middle layer of the allocortex has often been compared to layers V and the upper part of layer VI of the neocortex, because the cells (with somas) there usually extend their axons to other parts of the brain, as do most of those in the allocortex.^[25]

Very few cells of the allocortex (at least in turtles and lizards) make connections to other areas of the allocortex; they mostly talk to other regions of the brain. Thus, areas II and III of the neocortex, most of whose pyramidal cells send their axons to other parts of the neocortex,^[25] can reliably be considered new in mammals. That leaves areas I and IV, either of which might be compared to the outer layer of the allocortex, although there are differences in both cases. Axons coming from other regions of the brain usually terminate in layer IV of the neocortex, especially those coming from below, which would make this area comparable to the outer layer of the allocortex. Axons coming from other areas of the neocortex usually terminate in layer I, which would suggest that it's new. However, axons that crawl along the outside of the neocortex, most of which come from lower parts of the brain, probably interact with layer I in the same way that similar axons in the allocortex interact with its outer layer, which would imply some comparability there as well. It's well to remember that these comparisons are merely tools, artifacts of our need to use analogy to understand what's going on. Evolution is hardly constrained to fit within the categories we make for our convenience.

Before we consider the various connections into and out of the neocortex, let's take a look at the early evolution of the neural tube. This structure is inherited by vertebrates from their chordate ancestors, indeed recent research shows that the chordates themselves almost certainly inherited it from the earlier common ancestor of the echinoderms, hemichordates, and chordates.^[24] I have already suggested that concentration of nerves into a cord was primarily dependent on the availability of a circulatory system that could deliver enough oxygen to power their energy-dependent activity, a development that could have ramped up via the cold temperatures of the "snowball earth" conditions long before the Cambrian.

In chordates and their ancestors this oxygen was essential both to the neuropil, the system of nerve somas, neurites, and glial cells that performed calculations, and the axons which carried the results to other locations within the neuropil. However, in vertebrates we find Myelin, which insulates the axons and both increases the speed of impulses by perhaps an order of magnitude (or even more, depending on its thickness), and substantially reduces the energy requirements. This means that the primary requirement for energy was to the neuropil, the "grey matter", while the mass of axons, the "white matter" required much less.

In the original neural tube the neuropil was on the inside, while the axons were on the outside. This structure is almost certainly primitive, since it's carried over into the retina, where the reversed structure of the neural tube is expressed, and the nerves carrying information from light-sensitive cells actually travel over the surface of those cells (gathering and passing behind the retinal surface in the "blind spot"). In the spinal cord, it was developed into the standard structure of gray matter on the inside and white on the outside, which is very expandable, since most of the axons are traveling in a forward/backward (anterior/posterior) direction, and they are simply pushed farther apart (rather than lengthened) by expansion. Similarly, an expansion of the gray matter simply thickens it, with little impact.

In the front of the neural tube, things became a little more complex. Most of the primitive spinal cord was originally dedicated to controlling the actions of a body that was basically eel-like, swimming with an undulating movement, perhaps modifying it's motion with movements of the "fin-flaps" along each side of its body. Even when the "fin-flaps" came to be replaced with dedicated fins at the front and back, this just caused a small specialization of pre-existing bundles of ganglia, without impacting the effectiveness of the basic structure.

Figure 2: Five vesicle stage of embryo. (From DEVELOPMENT OF THE CENTRAL NERVOUS SYSTEM

But from the beginning, the brain was different. As you can see from figure 2, the di-encephalon has a pair of extrusions, which actually develop into the retinas. The olfactory system, OTOH, develops from the very front of the telencephalon. This puts the rest of the telencephalon between the optical system and the olfactory system. What does that mean?

For the earliest vertebrates (or chordates), swimming involved an undulatory movement that caused both the eyes and the nostrils to weave through the water. In order to identify whatever objects were seen in the water, their path in the visual system had to be integrated with the knowledge of the body's movement (coming from parts of the brain further back) to provide their location relative to the animal's actual path through the water. With chemicals diffusing through the water, the situation was more complex. Each object was emitting various chemicals that the olfactory system could sense, which diffused away from it subject to local currents and variations, until after a certain time it impacted the path of the nostrils (usually located at the very front of the animal) as they wove through the water. Thus the integration of olfactory cues with observed objects was a very complex problem.

In an earlier discussion I mentioned that even the earliest "swimming sponges" would have found a highly beneficial (speaking selectively) use for integrative intelligence, and the same holds true here. We can't estimate the intelligence of these animals, or this part of their brain, by the number of axons going into or coming out of it, because it might not take many axons to carry the information needed for the calculation, relative to the complexity of the calculation itself. But this would have made the region of the brain that later became the neocortex essential to the survival and prosperity of these animals, and when the necessary number of neurons and connecting axons grew, evolution provided the answer with the changes we observe in mammals.

If we fast-forward to the development of the earliest mammals, we find animals that used the three-layered allocortex for this process. At this time, the areas of the dorsal pallium primarily received input from other regions of the brain, especially those that would become the thalamus, and sent their output to other layers, also often (other parts of) the thalamus. Presumably, this part of the brain performed calculations that were, in effect, straight transformations: integrating and massaging incoming information to provide answer(s) that could be sent on for further use.

I've mentioned that in the allocortex inputs primarily arrived at the outer layer. Cells in the middle (and lower) layer had to make connections to them, which they did by extending a large dendrite, called the "apical dendrite", to the surface. What makes them pyramidal in shape (which gives them their name) is that they also extend smaller dendrites in other, lateral, directions, to receive inputs from other cells in their own layer. This tends to control the shape of the cell, which looks like a pyramid because each of these large dendrites tends to create a "corner" on the cell. The axon, with its axon hillock, tends to be much smaller, and doesn't really affect the shape of the cell. Pyramidal cells are the primary type of cell that send axons out of cortical area to other parts of the brain.

The other primary type of cell in these cell-rich layers are interneurons, which are usually inhibitory cells: unlike pyramidal cells (and stellate cells) they use a neurotransmitter (GABA) that tends to cause the target nerve cell not to fire action potentials rather than making it fire as excitatory cells do. Interneurons tend to have smaller arbors for both their dendrites and axons, although they often enough couple together via electrical (gap) junctions so that a single action potential can spread over quite a distance. They also usually migrate tangentially from other parts of the developing brain.^[25]

In mammals, as well as in dinosaurs and birds, the need for more complete integration of the various calculations, as well as more sophisticated time-dependent analysis, resulted in many further connections between various areas of the future neocortex. In the ancestors of dinosaurs, this led to the evolution of the wulst, a structure that has sometimes been compared to the neocortex, but has convincingly been shown to have developed independently.^{[4] [17]} In mammals, the neocortex evolved.

The early interconnections between cortical regions, in reptilian ancestors, went via the thalamus. However, to create a new intercortical connection via the thalamus it's necessary to create a new population of thalamic nerve cells, as well as processes to guide axons from these new cells to the target area of the cortex. Of course, a new population of pyramidal cells in the cortex is also necessary, which will sample the calculations going on in the neuropil and send the output via their axons to the appropriate spot. It's also necessary for guidance processes to evolve so that those axons can find their way to where their output is needed. But if the connection is directly cortical-to-cortical, these are all that are needed: nothing involving the thalamus is required.

The development of new cell types, with their new connections, depends critically on the six-layered structure of the neocortex. In this regard, I want to mention a recent paper, Cerebral cortex development: From progenitors patterning to neocortical size during evolution (by Alessandra Pierani and Marion Wassef), which unfortunately is behind a paywall. This paper surveys current knowledge of how pyramidal cell formation is regulated during the development of the neocortex. A key point is the specification of different subtypes destined for different layers:

The distinct laminar subtypes of neocortical neurons are born in a tightly regulated 'inside-out' sequence. The neurons destined to the deep layers are produced first followed by neurons fated to populate successively more superficial layers. Lineage tracing of single radial glia progenitors indicated that, at early stages, radial glia progenitors can produce successively the full repertoire of the major layer-specific neuronal types both in vivo and in vitro. Transplantation and cell culture experiments have, however, shown that the repertoire of the radial glia progenitors becomes progressively restricted ([refs]). The group of McConnell has shown that early cortical progenitors at the stage when they normally form layer VI neurons are multipotent and can generate later-born neurons of upper layer II/III, if exposed through transplantation to signals from a late cortical environment ([ref]). In contrast, later progenitors at the stage when they normally give rise to layer II/III neurons fail to produce deep layer neuronal types when transplanted to an early environment ([refs]).

This means that a complex interaction of transcription factors, and feedback loops among them, progressively tightens the ability of these progenitor cells to differentiate, limiting them to the current stage and later stages.

There have been some exceptions discovered to this pattern in rodents, which might complicate things, they are still under investigation.

There are also tight structures of transcription factors and loops among them that regulate the proliferation of early progenitor cells, controlling the ultimate area of each part of the neocortex. Pierani and Wassef also discuss the means by which the various parts of the neural tube are sectioned into regions such as the neocortex, and how the areas within it come to be defined. Gradients of various signalling molecules are built up, so the the ratio of these different molecules at any point is unique, after which a system of cross-repression divides the developing neural tube into specific regions, with gradients of signaling molecules within these regions which presumably allow incoming neurons to find their way to their specific target spot within the region involved.

Precisely how the new layers of the cortex, layers II and III, first arose can only be guessed at (at this point). It seems likely that the inside-out progression, and the tightly regulated system of distinct laminar subtypes described by Pierani and Wassef, evolved first, laying the groundwork for layers II and III. Once these layers were present, a new cell population could arise via mutation that targeted another cortical region, a far more likely (or less unlikely) event than depending on a thalamic relay. We can envision that the progressive evolution of the mammalian neocortex proceeded from this point.

We can see, then, that the neocortex, with its more sophisticated structure, allowed a substantial increase in the interconnectivity of the various regions of calculating neuropil, which in turn permitted the massive expansion of the brains, and intelligence, of the evolving mammals.

Alessandra Pierani, & Marion Wassef (2009). Cerebral cortex development: From progenitors patterning to neocortical size during evolution Development, Growth and Differentiation, 51 (3), 325-342 DOI: 10.1111/j.1440-169X.2009.01095.x

Links: (I've included only the link called out in this leader.) Not all of these are called out in the text, and too many are behind a paywall. Use the back key if you came via a footnote.

1. The evolution of the neocortex in mammals: how is phenotypic diversity generated? paywall

2. Genetic and epigenetic contributions to the cortical phenotype in mammals

3. Similarity and Diversity in Visual Cortex: Is There a Unifying Theory of Cortical Computation?

4. Do birds possess homologues of mammalian primary visual, somatosensory and motor cortices? paywall

5. The contribution of spike threshold to the dichotomy of cortical simple and complex cells paywall

6. Laminar processing in the visual cortical column

7. Neuronal circuits of the neocortex

8. The early differentiation of the neocortex: a hypothesis on neocortical evolution

9. Cortical mechanisms of action selection: the affordance competition hypothesis

10. Area Patterning of the Mammalian Cortex

11. Hagfish embryology with reference to the evolution of the neural crest paywall

12. Cyclostome embryology and early evolutionary history of vertebrates

13. Migratory neural crest-like cells form body pigmentation in a urochordate embryo paywall?

14. Brain and Behavior (IPHY 3730), University of Colorado at Boulder not peer-reviewed, but a good overview

15. Brain segmentation and forebrain development in amniotes paywall

16. Vertebrate head development: Segmentation, novelties, and homology paywall

17. Thoughts on the development, structure and evolution of the mammalian and avian telencephalic pallium

18. The emergence and evolution of mammalian neocortex paywall

19. The functions of the preplate in development and evolution of the neocortex and hippocampus paywall

20. Cortical Excitatory Neurons and Glia, But Not GABAergic Neurons, Are Produced in the Emx1-Expressing Lineage

21. Postnatal development of the telencephalon of the tammar wallaby (Macropus eugenii). An accessible model of neocortical differentiation paywall

22. Development of the olfactory system in a wallaby (Macropus eugenii) paywall

23. The Medial Pallium

24. Centralization of the Deuterostome Nervous System Predates Chordates paywall

25. Cerebral cortex development: From progenitors patterning to neocortical size during evolution paywall

Greening the Earth

2009-07-17T16:08:00.001-05:00

It's an interesting question, when did photosynthetic life first invade dry land, and what type was it? The tradition is that green plants first invaded the land in the Ordovician or Silurian, if not later, sometime after 500 MYA,^[7] well after the Cambrian, when we first see fossils of animals developing in the ocean (there are actually some from earlier, but those may not be animals, and we know little about them). However, there are various lines of evidence that there was already extensive land-based photosynthesis going on a good deal earlier,^{[3] [4]} including a very recent paper:^[2] The late Precambrian greening of the Earth (by L. Paul Knauth and Martin J. Kennedy, unfortunately behind a paywall), which examined the correspondence of ratios of carbon isotopes and oxygen isotopes in precambrian deposits, specifically from areas influenced by runoff from continents:

Here we compile all published oxygen and carbon isotope data for Neoproterozoic marine carbonates, and consider them in terms of processes known to alter the isotopic composition during transformation of the initial precipitate into limestone/dolostone. We show that the combined oxygen and carbon isotope systematics are identical to those of well-understood Phanerozoic examples that lithified in coastal pore fluids, receiving a large groundwater influx of photosynthetic carbon from terrestrial phytomass. Rather than being perturbations to the carbon cycle, widely reported decreases in ¹³C/¹²C in Neoproterozoic carbonates are more easily interpreted in the same way as is done for Phanerozoic examples. This influx of terrestrial carbon is not apparent in carbonates older than ~850 Myr, so we infer an explosion of photosynthesizing communities on late Precambrian land surfaces. As a result, biotically enhanced weathering generated carbon-bearing soils on a large scale and their detrital sedimentation sequestered carbon. This facilitated a rise in O₂ necessary for the expansion of multicellular life.

This analysis basically plotted the isotope ratios from thousands of observations on a two-dimensional axis, and observed that those from after about 850MYA fell into the same groups whether they were after the beginning of the Cambrian or before. This leads to the very plausible conclusion that photosynthesizers had colonized the land and were producing large amounts of carbon-rich detritus that was then oxidized and deposited.

This has some interesting implications: ...

The contrasting isotope data between 850 Myr ago and the Neoproterozoic suggest that the terrestrial expansion of photosynthesizing communities preceded the significant climate perturbations of the late Precambrian glaciations, and was followed by a rise of O₂ ([ref]) and a secular change in terrestrial sediment composition. The onset of significant biotically enhanced terrestrial weathering would have increased the flux of lithophile nutrient elements and clay minerals to continental margins. This would have increased production and burial preservation of organic C towards modern values and consequently facilitated the stepwise rise in atmospheric O₂ necessary to support multicellularity. The terrestrial expansion of an extensive, simple land biota indicated by the isotope data may thus have been a critical step in the transition from the Precambrian to the Phanerozoic world.

The biggest problem with this is the lack of fossils identifiable as from plants, although the "squishier" plants leave few fossils.

There is one very important feature of plants that allowed them to colonize the land: the invention of mixtures of lignin and cellulose that protects them against the "soft" ultraviolet radiation (UV) that makes it through the ozone layer. This mixture, in turn, depends on a synthesis pathway that begins with an enzyme called Phenylalanine Ammonia Lyase (PAL), "which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes."^[8]

Another very recent paper, A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land (by Giovanni Emiliani, Marco Fondi, Renato Fani, and Simonetta Gribaldo) reports an intriguing discovery: that the gene for this enzyme was almost certainly acquired via horizontal gene transfer from a soil bacterium, or perhaps from a fungus that had in turn acquired it from a soil bacterium. What they did was to examine the phylogenetic tree of "160 representative sequences" from various species, discovering that all the genes in plants and fungi are descended from a single ancestor related to those of one bacterial lineage. This gene "is homologous to histidine ammonia lyase (HAL), which is involved in the catabolism of histidine and is widespread in prokaryotes and eukaryotes [refs]. It has been proposed that "PAL developed from HAL when fungi and plants diverged from the other kingdoms" [ref]. However, the current view of eukaryotic evolution based on phylogenetic analyses indicates that fungi and plants do not share an exclusive ancestor [refs]. In fact, Fungi are more related to Animals than to land plants. Moreover, land plants belong to the phylum Plantae, which also includes Glaucocystophytes, red algae, and green algae [refs]."

Figure 1: Phylogenetic tree of HAL/PAL gene. Click on image to see original with caption. (From Ref 8 Figure 2)

This, combined with the observations of Knauth et al., brings us to an interesting suggestion: is it possible that, before green plants invaded the land, it was covered with lichens? Lichens, even today, often grow in areas that are heavily exposed to sunlight (UV) but lack the soil necessary for plant roots (and their symbiotic association with certain fungi). Absent plants, they may well have been able to colonize just about any area with sufficient rainfall to provide the water they needed. Lichens are known to invade rock for nutrients,^[6] and even cyanobacteria, one of the groups of algae that for symbiotic relationships with fungi to create lichens can chemically erode rocks.^[5] The possibility that there was a coating of lichens over most of the Earth's surface as long as 850MYA is quite intriguing.

An obvious question is: what, if anything, ate these lichens? Here I want to hark back to a suggestion I made a while back, regarding the origin of multi-celled animals, and probably other forms of life:

Could it be that the common ancestor of fungi and animals was actually multinucleate, an amoeba-like creature with lots of nuclei, a flexible shape, and a feeding pattern based on engulfing its food?

Such a creature would be well positioned to evolve into both fungi and metazoans, with the latter branch having lots of collared flagelli. The question is, why evolve multiple cells? The answer could well be an explosive adaptive radiation of invasive, intracellular predators. Such an explosion would explain the sudden acquisition of multicellularity by many lineages.

It isn't just animals and fungi that would be so descended, and it's quite possible that a variety of multinucleate amoeboids were present in these early times that fed on the early lichens I've proposed. (Indeed, there are many such today. These may well have lived in small, shaded tunnels during the day (when solar UV may well have threatened them), and come out at night to feed on the upper levels of the lichens. The lichens themselves may have used some form of lignin (or dyes depending on PAL for synthesis) to protect themselves from the sun, although another possibility is that they shed their upper levels as they were damaged, regrowing from cells located deeper, where they were protected from UV. Or it could have been a combination of both.

The possibility that there was a full-blown ecosystem present on the land this long before the Cambrian offers exciting possibilities in understanding the earliest evolution of the animals (in the ocean), as it would have provided large quantities of detritus for food, along with the oxygen needed to take advantage of it. Especially important is that it this would have been true during the two proposed eras of "snowball earth" or "Slushball Earth", when glaciation extended quite far towards the equator: large areas of the earth's coastline would have experienced freezing temperatures along with intense sunlight.

This is important because water close to the freezing point can actually contain enough oxygen to function as blood in an animal that isn't too active, unlike warmer water. This means that animals during those periods might have invented sophisticated circulatory systems, carrying oxygen for all their needs, without the need for cells containing haemoglobin or some other compound specialized for carrying larger amounts of oxygen. By the time the glacial ages were over, presumably some lineages (at least of chordates) had already developed blood cells containing haemoglobin, thus kicking off the chordate/vertebrate adaptive explosion.

Knauth, L., & Kennedy, M. (2009). The late Precambrian greening of the Earth Nature DOI: 10.1038/nature08213

Emiliani, G., Fondi, M., Fani, R., & Gribaldo, S. (2009). A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land Biology Direct, 4 (1) DOI: 10.1186/1745-6150-4-7

Links: (I've included only those links called out in this leader.)These are almost all behind paywalls, unfortunately. I wish they weren't, but...

1. Plant-driven fungal weathering: Early stages of mineral alteration at the nanometer scale paywall

2. The late Precambrian greening of the Earth paywall

3. Late Precambrian Oxygenation; Inception of the Clay Mineral Factory free registration required

4. Molecular Evidence for the Early Colonization of Land by Fungi and Plants free registration required

5. Effect of cyanobacterial growth on biotite surfaces under laboratory nutrient-limited conditions paywall

6. Mineralogical transformation of bioweathered granitic biotite, studied by HRTEM; evidence for a new pathway in lichen activity paywall

7. The early development of terrestrial ecosystems

8. A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land

Concepts, Cognition, and Anthropomorphism

2009-07-14T13:53:00.001-05:00

Ever since Plato, western philosophers have looked at words, and the objects they represent, as a sort of fixed ideal: the word "couch", for instance, represents an object, or rather one of a class of objects. Lately, in the last few centuries, scientists and/or philosophers have recognized that the same word might represent different, but widely overlapping, classes under different circumstances (contexts), a fact that often leads to confusion, sometimes deliberate. All of this tends to focus attention on the relationship between words and symbols, strengthening the notion that humans are the only "Symbolic Species", since the evidence is overwhelming that no other species (with a few possible cetacion exceptions) uses language in anything like the way we do.

But is that true? How closely are symbols, and the concepts they represent, tied to language and the use of words as symbols? For that matter, what is a symbol, in terms of cognition, or the mechanics of our brains?

Before we explore these questions, let's back up and take a look at the context: the paradigm within which we are asking these questions, understanding what they mean, and judging the answers.

It began with Plato, as mentioned above. From his work we get the concept of the Platonic Ideal: the perfect representation, the archetype, behind a concept represented by a word. As he explained it, we are chained in a cave as it were, looking at the back wall, able to see only shadows cast by the ultimate, ideal, reality cast by the light of "Truth", because we are unable to turn and look out the entrance.

This paradigm was pretty much universal by Hellenistic times (a few centuries after Plato) in the west, and also, I suspect, in the east where it had spread via Persion/Greek influences to India, and from there via Chan/Zen Buddhism (and possibly other schools) across North Asia to China. (My suspician is partly founded on the fact that Zen Koans seem well designed to break the tyranny of words/concepts as absolutes, forcing the seeker to recognize that these things are only limited tools, like a set of shelves which are fine for holding small solid objects, but limited for very large objects and useless for liquids.)

The reality, as recent research is showing, is that our brains typically identify words heuristically: we learn of a number of items that belong to a class represented by a word, our minds (often subconsciously) identify common features or characteristics of these items, and we tentatively identify new members of the class based on those same shared features/characteristics. ...

Backing up again to Plato, we can see that there's no reason that such classes require an "ideal" at all: they are just groupings of items that are all similar enough to justify attaching a word, a symbol, to the class. A concrete example may be helpful: consider the word "couch". This may be loosely defined as a bench with a back and armrests (at least in modern usage), long/wide enough for at least two people to sit comfortably. Can we define a Platonically ideal couch? Not without context. For instance, to Victorians such a couch would have had a reasonably vertical back and stiff cushions, helping to support people who were expected to sit up with good posture while socially interacting. But for modern laid-back music lovers, the ideal couch will be much more relaxed, allowing occupants to lean back and totally relax while losing themselves in musical reproductions not available even live to Victorians.

Thus, the ideal, singular to Plato, splits into many depending on context, observer, and time. The problem is that our thought patterns, our paradigms, are constrained by over two thousand years of Plato's influence, and they often interfere with efforts to understand how language, symbols, and concepts work.

It's certain that the human brain has a mechanism for representing words: my best guess is that they're normally represented (in at least one area of the brain) as abbreviated "shorthands" for the sequence of tongue, lip, mouth, throat, and diaphragm movements that go into pronouncing them. But is this true of concepts? Did recent human ancestors invent the concept, or the symbol that stands for it? Are even our closest relatives lacking this feature?

I think not. We know that many primates possess "mirror neurons", pyramidal cells in parts of the neocortex that tend to fire in the same groups when the animal is performing (or preparing to perform) some action and when it's observing some other animal performing that action. I would say that actions of this sort represent concepts, and that the processes around the firing of these "mirror neurons" represent neurological symbols (or the use of them). At a sufficiently abstract level, there's no real difference between a specific pattern of lines on a piece of paper (or clay) and a specific pattern of neurons in the neocortex (or a specific pattern of sounds).

Before we go farther, we need to examine how the mammalian neocortex operates. I'm going to use Francis Crick's Astonishing Hypothesis as a base, although it's highly simplistic and probably wrong in some details. As he does, I'm going to focus on the V1 area in the visual cortex, which receives input from the retina (via the lateral geniculate nucleus: a part of the thalamus), performs a complex transformation on it, and sends the results on to further areas of the brain.

The large majority of axons coming from the retina carry a single type of message: each neuron is watching a specific location in the retina, looking for a specific type of spot against an opposite background: some look for big spots, some for small. Some for dark spots (against a light background), some for light. some for red spots (against a presumably green background), some for blue, green, purple, etc. Now all of these things these different neurons are looking for can be mapped onto an n-dimensional space: in this case with n probably equal to five: two dimensions for the location within the retinal field, one for size, one for color, and one for light/dark. The light/dark axis may be discrete rather than continuous; it may even be two-valued. The color axis also may be somewhat more complex than my simple description makes it sound: there are some complications regarding the distribution of cone types within the retina that time and space don't permit discussing. These points don't affect the basic picture: the visual field of the retina can be mapped as an n-dimensional space of "spots" with each neuron sampling a specific location in that space and responding accordingly.

Of course, most of the visual field isn't made up of spots (although in the world of the earliest chordates it may well have been: our evolutionary history is often built into our design in ways we wouldn't suspect). What each neuron in the retinal population I'm discussing does is look to see how much the visual input resembles the type of spot it's looking for, and the more it does, the larger its firing rate (the faster it fires action potentials). Notice, then, that what we have here is a continuous function over a continuous space (disregarding complications involving a discrete light/dark axis) varying continuously over time, but sampled at discrete points in space and time. Each neuron occupies a specific point in the n-space and samples that one point (although since it's actually examining the vicinity looking for a spot, one close to its location would generate a partial signal). Each neuron intermittently sends a signal with its instantaneous firing rate, thus the closer it is to seeing what it's looking for, the more frequently its signal is being sampled.

What does the V1 area do with this information? The major populations of pyramidal cells look for bars: wide bars, thin bars, vertical bars, horizontal bars, dark bars, light bars, red, blue, green, purple, etc. And everything in-between. The information brought from the retina (relayed via the lateral geniculate nucleus) is integrated and messaged by the cortical neuropil and the stellate cells of layer IV, eventually allowing the pyramidal cells to sample an n-dimensional space of bars and send their signal accordingly. (Actually, the situation is more complex because these cells are also looking for time-dependent patterns as well, but if they can support the more complex situation, they can certainly support the simpler one.)

Are we beginning to see a pattern here? Nerve cells in at least two parts of the brain can, in effect, occupy a discrete location in some n-dimensional space, sample a scalar signal at that location, and output the results to their axons, whence it's carried to other parts of the brain. (The vertebrate retina is part of the brain developmentally: it starts out as part of the neural tube and is then drawn away into the eye structure. It's not part of the neocortex, however, the retina had differentiated and specialized a long time before the ancestors of mammals invented the neocortex.^[1])

We don't need, here, to go into how this process is achieved: it's enough to know it can be done. And what one area of the brain can do, so can any other: whatever the mechanism, it's almost certainly reusable. (Note, however, that just because this mechanism is available to every part of the brain doesn't mean every part of the brain uses it. OTOH when we're looking for a mechanism to explain some observation, it is an obvious candidate.)

Let's get back to our "concepts" within the brain represented by specific groups of neurons (such as "mirror neurons") firing when a specific "concept" is called to mind in an animal, either by seeing some other animal performing an action or by performing, or preparing to perform, that action. Based on the description above, it's a good guess that those neurons occupy a specific location in some n-dimensional "concept space" that corresponds to the specific act involved. Of course, since at this level of consciousness humans, and probably other primates, normally pay attention to only one general subject at a time, it may be that each individual concept is represented by a unique pattern: sort of like an ideogram but in n dimensions rather than just two.

Figure 1: Cursive hieroglyphs (a type of ideogram) from the Papyrus of Ani, an example of the Egyptian Book of the Dead. (From Wiki)

At this point I want to discuss some very recent research: Mirror Neurons Differentially Encode the Peripersonal and Extrapersonal Space of Monkeys ( by Vittorio Caggiano, Leonardo Fogassi, Giacomo Rizzolatti, Peter Thier, Antonino Casile), which is unfortunately behind a paywall, but let me blockquote the abstract:^[3]

Actions performed by others may have different relevance for the observer, and thus lead to different behavioral responses, depending on the regions of space in which they are executed. We found that in rhesus monkeys, the premotor cortex neurons activated by both the execution and the observation of motor acts (mirror neurons) are differentially modulated by the location in space of the observed motor acts relative to the monkey, with about half of them preferring either the monkey's peripersonal or extrapersonal space. A portion of these spatially selective mirror neurons encode space according to a metric representation, whereas other neurons encode space in operational terms, changing their properties according to the possibility that the monkey will interact with the object. These results suggest that a set of mirror neurons encodes the observed motor acts not only for action understanding, but also to analyze such acts in terms of features that are relevant to generating appropriate behaviors.

Unlike many abstracts, this one is pretty easy to understand, and its implications are extremely relevant to the subject here. The "mirror neurons" under examination are associated with motor activity, and may well be associated with a system of representing "concepts" with shorthands of motor sequences.

I mentioned above that in my view the representation for words in the human brain is some sort of "shorthand" for the sequence of muscle actions involved in pronouncing it; similarly it makes sense that in monkeys, apes, and other primates with "mirror neurons" the representation in at least one area of the brain for "concepts" involving actions is a similar shorthand for the muscle actions involved. Or rather, the shorthand in primates came first, and the process was adapted for use with language by adding specific tongue, lip, mouth, throat, and diaphragm movements to a system already adapted for arm, leg, hand, and foot movements.

In trying to understand how "concepts" are represented in the brain, we need to consider how they're used. As Caggiano et al. point out, the relevance of an action undertaken by another depends (in kind as well as quantity) on the distance of that other, and it makes sense that the specific "concept" activated in the brain is slightly different depending on that distance. Rather than trying to separate these different reactions into completely separate concepts, perhaps we should think of this as more like adverbs modifying a verb: the same action stimulates the same concept, but the distance, both absolute and operational, stimulates distinct modifying adverbs. Of course, we must also keep in mind that this research looked at only one area of the brain, and that one being associated with motor activity, specifically the planning and execution of such activity.

We need to keep in mind that the brain is made up of many areas, all talking to one another: in rhesus monkeys there are 52 areas just on each side of the neocortex, this may also be the number for humans, although the detailed research needed to prove it hasn't been done yet for ethical reasons. There may be, probably are, more than one area involved in expressing these "concepts", and each area probably uses a different system of representation. Exactly how these areas express their concepts, and the precise relationships among expressions in different areas, is a subject for future research. However there are some things we can be fairly sure of from what we know already.

For one thing, the brain appears to operate on a very associational basis: if one area is stimulated to "fire" a certain concept it will likely stimulate other areas to fire the same concept. Some of these areas may act to relate concepts to one another, others may act to related observations of other animals to various concepts that classify their actions, yet others may act to relate concepts for proposed actions to specific conditions such as food lying on the ground nearby or hanging from a nearby branch, yet others may serve to react to various concepts with responses from memory regarding past incidents where similar actions took place in similar circumstances. The relationship among these various areas may then allow a decision regarding whether, and how, to undertake the action this concept represents.

Again quoting from Caggiano et al., this time from the conclusion:^[3]

Our results suggest a cognitive role for mirror neurons as a system that not only encodes the meaning of observed actions but also contributes to choosing appropriate behavioral responses to those actions. In particular, a stimulating (although admittedly speculative) interpretation of our results is that mirror neurons not only may represent a neuronal substrate for understanding "what others are doing," but also may contribute toward selecting "how I might interact with them."

Notice that in all this I've essentially expanded the use of "concepts" to all primates possessing "mirror neurons". This makes sense, since if the firing of a certain pattern of neurons in even one area of the brain represents an attentional focus on one particular idea, such as a class of actions, it makes a valid symbol, and symbols can be reasonably considered to represent concepts. Language doesn't come into it. Or rather, language came into it very late in the game, when one lineage of apes came to represent a well-established system of symbolism within the brain with something that could be easily communicated to other members of the local group.

Thus we can see that while language is very likely (but not certain) to be a human invention, the use of symbols, and the concepts they represent, is probably much older: language certainly added a dimension or more to the utility and effectiveness of symbols and concepts, but the original system was in place at least tens, and possibly hundreds, of millions of years earlier.

Caggiano, V., Fogassi, L., Rizzolatti, G., Thier, P., & Casile, A. (2009). Mirror Neurons Differentially Encode the Peripersonal and Extrapersonal Space of Monkeys Science, 324 (5925), 403-406 DOI: 10.1126/science.1166818

Links: Not all of these have been called out in the text. Use the back key if you came via clicking a footnote.

1. The Early Differentiation of the Neocortex: a Hypothesis on Neocortical Evolution

2. Genetic and epigenetic contributions to the cortical phenotype in mammals

3. Mirror Neurons Differentially Encode the Peripersonal and Extrapersonal Space of Monkeys paywall

Encephalon 73 is Up

2009-07-13T14:56:00.000-05:00

With three of my better (IMO) posts, along with a great line-up. Each post is accompanied by a video searched out by the editor, Sandra Kiume. See it here.