Transcriptomics of the fetal human brain

A cutting-edge application of the Affy total human exome GeneChip (4X coverage per exon, 40X coverage per gene): Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis.

From the News and Views, I was intrigued to learn that previous transcriptome analyses of adult human brains found very little difference in gene expression between brain areas:

[…] this suggests that it is the gene expression during development that largely determines higher brain functions by specifying the complexity of neural connections. Numerically, the most important genes relating to cognitive differences between species may be genes that specify how the machinery is put together. In support of this hypothesis, many of the identified differentially expressed genes in this study are related to processes involved in connection formation, such as axonal guidance and cell adhesion.

An impressive 76% of all human genes are expressed in the developing fetal brain. Of those, 33% are differentially expressed over brain regions (13 regions were examined) and 28% are alternatively spliced. The differentially expressed genes are also ones that seem to have evolved the most recently. Even in these early (midgestation) stages, left-right asymmetry was seen, such as the localization of the language-associated FOXP2 genes to Broca’s area.

Of interest to computational folks, they find that gene expression follows power-law scaling (as many other naturally occurring “small-worlds” networks do) with certain hub genes connected to many others and certain spoke genes with relatively few connections. Unsupervised hierarchical clustering is used in this analysis.

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Futurist or random number generator?

Hmmm…
Ray Kurzweil from Salon/bigthink.com on simulating the human brain:

http://images.salon.com/video.swf?id=w-79167-2016605

I think he might be right that we can simulate the brain before we understand it, however.

sCRACM: ChR2 circuit mapping

As has become a hallmark of the Svoboda lab, this new paper in Nature (advance online publication) combines several cutting edge technologies (rAAV-delivered ChR2, most prominently, and 2-photon 1-photon laser stimulation) to do some interesting synaptic physiology.

The subcellular organization of neocortical excitatory connections : Article : Nature.

They used ChR2 (with TTX and 4-AP to block action potentials) to find where on the dendritic tree particular inputs synapsed onto L3 and L5 cells and to measure the strength of those inputs. ChR2 depolarizes the input axon locally (60um spot diameter) at points of (potential) axodendritic contact. If you’ve heard the term “potential synapse” before, then think of this technique as a way of checking potential synapses and seeing if there really is an actual synapse there.

The technique allowed them to map on a L3 barrel cortex pyramidal cell where different thalamic inputs (VPm, POm) and cortical inputs (M1, barrel L2/3, barrel L4):

screenshot001

sCRACM stands for subcellular ChR2-assisted circuit mapping.

Neuroscience of voting

As the first presidential debate nears, there’s a lot of excitement (and worry) regarding the election. Today, Salon had an interesting piece on voter behavior and irrational attachment to ideologies and candidates. Recounting a recent psychology paper’s punchline:

The article’s conclusion should be posted as a caveat under every political speech of those seeking office. And it should serve as the epitaph for the Bush administration: “People who lack the knowledge or wisdom to perform well are often unaware of this fact. That is, the same incompetence that leads them to make wrong choices also deprives them of the savvy necessary to recognize competence, be it their own or anyone else’s.”

Slate had a story (“Why is every neuropundit such a raging liberal?“) about how neuroscience and neuromarketing are changing political consulting (also here’s a link to a similar story in NYT last week):

According to a study of political psychology published last Thursday in Science, conservatives tend to be the jumpier lot.

The researchers called 46 political partisans into their laboratory at the University of Nebraska, affixed electrodes to their fingertips and eyelids, and measured sweat output and eye blinks in response to a series of startling stimuli. (Subjects were forced to endure images of bloody faces and maggot-infested wounds, as well as sudden blasts of white noise.) The results: Social conservatives—those who supported the death penalty, the Patriot Act, prayer in school, and the like—sweated more, and blinked more intensely, than the liberals.

The Slate and NYT articles in particular suggest something that I have long believed to be true. The Republican “story” is, from a neuroscience perspective, simply better because it tends to view the world in clear-cut terms with no middle ground and, thus, is more effective at rallying emotional processing areas of the brain (eg. limbic system). It is well-known in neuroscience that emotionally salient events that activate these limbic structures are better remembered than less charged memories. The Democratic “story” tends to be more complicated with shades of gray and therefore requires higher-level processing (eg. cortical areas involved in conflict resolution). Clearly, I’m oversimplifying things here a bit (see, I’m designing this post to appeal to your limbic system!) but I think that this hypothesis might have some legs.

Of course, if it’s true, why doesn’t everyone vote Republican if that story is the neurally more rewarding one? Or perhaps the more relevant question: Is it even possible for the Democrats to tap into the similar evolutionarily older limbic structures that seem to dominate the Republican story?

Also, although I prefer Neurodudes to stick with the science over any partisan politics, I must say I found this statistic interesting (from the Slate article):

in 2002, Daniel Klein and Andrew Western tallied the political affiliations of professors at Berkeley and Stanford and found that even in the hard sciences, Democrats outnumbered Republicans by a factor of almost 8 to 1. Among professors of neurology and neuroscience, Klein and Western counted 68 registered Democrats against just six Republicans.

A Computational Neuroanatomy for Motor Control

An extremely interesting trend in neuroscience has been to use the language of Control Theory to explain brain function. A recent paper by Shadmehr and Krakauer does a very nice job of summarizing this trend and assembling a comprehensive theory of how the brain controls the body. Using control theory, they put forward a mathematically precise description of their theory. Because their theory uses blocks that are direct analogues of specific brain regions like the basal ganglia, motor cortex, and cerebellum, they can use brain lesion studies to undergird their ideas about these components. From the paper:

The theory explains that in order to make a movement, our brain needs to solve three kinds of problems: we need to be able to accurately predict the sensory consequences of our motor commands (this is called system identification), we need to combine these predictions with actual sensory feedback to form a belief about the state of our body and the world (called state estimation), and then given this belief about the state of our body and the world, we have to adjust the gains of the sensorimotor feedback loops so that our movements maximize some measure of performance (called optimal control).

At the heart of the approach is the idea that we make movements to achieve a rewarding state. This crucial description of why we are making a movement, i.e., the rewards we expect to get and the costs we expect to pay, determines how quickly we move, what trajectory we choose to execute, and how we will respond to sensory feedback.

This approach of describing brain lesion studies in the context of a well-thought out theory ought to be further encouraged.