Wednesday, July 26, 2006

Spindle Neurons: The Next New Thing?

In a neuroanatomical tour de force, Nimchinsky and colleagues (1999) obtained access to samples of the anterior cingulate cortex (and other cortical regions) from 28 different primate species, from prosimians to anthropoids to great apes to humans. They processed the samples with a Nissl stain to identify neuronal cell bodies in the cerebral cortex, a structure that (generally) consists of six layers. Spindle neurons are a unique type of neuron found in layer Vb in the ACC and frontoinsular cortex of humans. This is nothing new; spindle neurons (also called Von Economo neurons) were first identified in the 19th century by W. Betz (of the eponymous Betz cell fame, I presume) and by Nobel laureate Santiago Ramón y Cajal. What was new in 1999 was the finding that only humans and great apes have spindle neurons.

Nimchinsky EA, Gilissen E, Allman JM, Perl DP, Erwin JM, Hof PR. (1999). A neuronal morphologic type unique to humans and great apes. Proc Natl Acad Sci 96:5268-73.

We report the existence and distribution of an unusual type of projection neuron, a large, spindle-shaped cell, in layer Vb of the anterior cingulate cortex of pongids and hominids. These spindle cells were not observed in any other primate species or any other mammalian taxa, and their volume was correlated with brain volume residuals, a measure of encephalization in higher primates. These observations are of particular interest when considering primate neocortical evolution, as they reveal possible adaptive changes and functional modifications over the last 15-20 million years in the anterior cingulate cortex, a region that plays a major role in the regulation of many aspects of autonomic function and of certain cognitive processes. That in humans these unique neurons have been shown previously to be severely affected in the degenerative process of Alzheimer's disease suggests that some of the differential neuronal susceptibility that occurs in the human brain in the course of age-related dementing illnesses may have appeared only recently during primate evolution.

Here's what John Allman's Lab at Cal Tech says about their work:
Our lab has investigated the anatomical structure of the Von Economo (spindle) neurons in anterior cingulate and fronto-insular cortex. Based on functional imaging studies of these brain areas and our studies of the expression of neurotransmitter receptors on these cells, we think they participate in fast, intuitive social decision-making. We have found that the Von Economo neurons emerge mainly in the first three years after birth. We also have evidence that in autistic subjects the Von Economo neurons are abnormally located, possibly as a result of a migration defect. This abnormality may be at least partially responsible for defective social intuition in autism.
Somehow, the "spindle neuron" meme hasn't caught on like the "mirror neuron" meme. Is it because spindle neurons have been only been described anatomically (not physiologically), while the reverse is true for mirror neurons? Anatomically speaking, do we know much about mirror neurons? Here's what Rizzolatti and Craighero (2004) have to say about them:
Mirror neurons are a particular class of visuomotor neurons, originally discovered in area F5 of the monkey premotor cortex, that discharge both when the monkey does a particular action and when it observes another individual (monkey or human) doing a similar action (Di Pellegrino et al. 1992, Gallese et al. 1996, Rizzolatti et al. 1996a).

from Rizzolatti G, Craighero L. (
2004). The mirror-neuron system. Annu Rev Neurosci. 27:169-92.
In the elegantly titled article, The importance of being agranular, Stewart Shipp reviews evidence that approximately 10% of recorded cells in premotor area F5 in the macaque monkey can be classified as mirror neurons. He also points out an interesting conundrum regarding the anatomical organization of motor cortex: it's agranular, meaning it's lacking the granule cell layer (layer IV), the typical termination point for feedforward sensory information. Area 7b (or PF) in the rostral inferior parietal lobule provides the main parietal input to F5. Without going into too many details, it seems the anatomical circuitry of visual input to F5 is pretty complicated. Anyone who studies mirror neurons (or who does fMRI studies of "empathy and the mirror neuron system") should read these two papers:
Geyer S, Matelli M, Luppino G, Zilles K. (2000). Functional neuroanatomy of the primate isocortical motor system. Anat Embryol 202:443-74

Shipp S. (2005). The importance of being agranular: a comparative account of visual and motor cortex. Philos Trans R Soc Lond B Biol Sci. 360:797-814.

Gap ad, with mirror neurons by Rizzolatti & Craighero (2004)

Everybody's talking about mirror neurons!!

Con: Mixing Memory and Neurotopia (version 2.0)

Mirror Neurons, Language, and Meaning (Oh, My!)

Everybody Post About Mirror Neurons!!!

Less Con: The Frontal Cortex

Are Mirror Neurons Too Cool?

Pro: Small Gray Matters

Mirror neurons aren’t really all that bad…

ADDENDUM: and there's more!

Neurofuture: Mirror meme

Mind Hacks: Reflected glory

And the post that really started it all,

BrainTechSci: Much Ado About Mirror Neurons

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At March 17, 2007 7:14 AM, Blogger Joe said...

I want to put in a plug for collaborative efforts in comparative neurobiology. I participated in the project in which Nimchinsky, Hof, et al. (1999) discovered that spindle (von Economo) neurons occur in orangutans, gorillas, chimpanzees, and bonobos, as well as humans. This certainly stimulated additional work by Allman and his students, as well as Hof, his students, and colleagues. I just attended a meeting in Cambridge, Mass, where Tania Singer reported on her fMRI work with humans, where she again described how anterior insula light up in response to stimuli intended to arouse empathy, etc. These areas, of course, are bilateral, but the intensity of the response appeared to me to be very lateralized from the images she showed. Independent evidence of lateralization of insular function exists, and even though she said she did not see lateralization, it was so obvious I think there needs to be another look. These VEN-rich areas seem to be involved in what I would describe as "evaluation" and decision making based on comparisons of values. Since there is much individual variation in values held and value judgements, it seems important to pay much attention to individual differences in studies of this kind, and this seems especially important not only to our understanding of human consciousness, but seems fundamental to the developing field of neuroeconomics.

At November 27, 2007 6:19 AM, Anonymous Anonymous said...

huh? neuroeconomics...?
was is dat? ... 'Josephs' blog is 'inaccessible'...
Otherwise, overall, interesting reading .... thanks....

At November 09, 2012 9:55 AM, Anonymous Jonathan W. Maxson said...

Very helpful article. Thank you so much. You might be interested in reading this:

Aside: Freya's Distaff, the Spindle of Fate and a Spindle Neuron Hypothesis.


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