Giving up? Your parvalbumin neurons may have something to do with it

Cartoon from http://i393.photobucket.com/albums/pp20/saisi24/dontgivedup.jpg, licensing unknown
Cartoon from Photobucket, licensing unknown.

One of the most ecologically-valid rodent models of depression is the learned helplessness paradigm. You get a rat or a mouse and you confine it in a cage with an electrified grid. Then you apply mild foot shocks at random intervals and of random duration for an hour (which is one session). The mouse initially tries to escape, but there is no escape; the whole floor is electrified. After a couple of sessions, the mouse doesn’t try to escape anymore; it gives up. Even when you put the mouse in a cage with an open door, so it can flee to no-pain freedom, it doesn’t attempt to do so. The interpretation is that the mouse has learned that it cannot control the environment, no matter what he does, he’s helpless, so why bother? Hence the name of the behavioral paradigm: learned helplessness.

All antidepressants on the market have been tested at one point or another against this paradigm; if the drug got the mouse to try to escape more, then the drug passed the test.

Just like in the higher vertebrate realm, there are a few animals who keep trying to escape longer than the others, before they too finally give up; we call these resilient.

Perova, Delevich, & Li (2015) looked at a type of neuron that may have something to do with the capacity of some of the mice to be resilient; the parvalbumin interneurons (PAI) from the medial prefrontal cortex (mPFC). These neurons produce GABA, the major inhibitory neurotransmitter in the brain, and modulates the activity of the nearby neurons. Thanks to the ability to genetically engineer mice to have a certain kind of cell fluoresce, the researchers were able to identify and subsequently record from and manipulate the function of the PAIs. These PAIs’ response to stimulation was weaker in helpless animals compared to resilient or controls. Also, inactivation of the PAI via a designer virus promotes helplessness.

Reference: Perova Z, Delevich K, & Li B (18 Feb 2015). Depression of Excitatory Synapses onto Parvalbumin Interneurons in the Medial Prefrontal Cortex in Susceptibility to Stress. The Journal of Neuroscience, 35(7):3201–3206. doi: 10.1523/JNEUROSCI.2670-14.2015. Article | FREE FULLTEXT PDF

By Neuronicus, 21 October 2015

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I’m not like you, inside and out

Credit: Dawn of the Planet of the Apes
Screenshot from “Dawn of the Planet of the Apes” (Director: Tim Burton, 2001)

One mistake than many neuroscientists make (myself included) is the implicit assumption that the human brain is a rodent brain scaled-up, plus a few more bits. Here is a remainder that “a rat is not a monkey is not a human”, in the famous words of A. D. (Bud) Craig (2009).

Mohan et al. (2015) analyzed a portion of the brain (Brodmann area 21) obtained from 28 individuals that had to undergo neurosurgery and have it removed for various illnesses. Using some good microscopy, fancy statistics, and 3-D modeling, they reconstructed the shape of individual neurons from that region. The main finding is that 88% of human pyramidal neurons were distinctly different than their mouse or macaque counterparts. Also, they managed to record the electrical activity of these neurons in less than 10 minutes after resection. So it appears that this morphological distinctness of ours results in unique electrical properties of human neurons, which may account for the “distinct cognitive capabilities of humans”, as the authors put it.

Approximate location of Brodmann Area 21, corresponding to gyrus temporalis medium. Credit: Brain template to _DJ_; Area tracing to Neuronicus
Approximate location of Brodmann Area 21, corresponding to gyrus temporalis medium. Credit: Brain template to _DJ_; Area tracing to Neuronicus

Citation: Mohan, H., Verhoog, M. B., Doreswamy, K. K., Eyal, G., Aardse, R., Lodder, B. N., Goriounova, N. A., Asamoah, B., B. Brakspear, A. B. C., Groot, C., van der Sluis, S., Testa-Silva, G., Obermayer, J., Boudewijns, Z. S., Narayanan, R. T., Baayen, J. C., Segev, I., Mansvelder, H. D., de Kock, C. P. (28 August 2015; Epub ahead of print). Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex. Cerebral Cortex, 1-15. doi: 10.1093/cercor/bhv188. Article + FREE PDF