Tuesday, April 19, 2011

Dumb again and knowing it

Starting a post-doc is frustrating.  Two months ago in my graduate lab, I was able to perform experiments by myself, analyze the data quickly, and fit it into a larger picture.  Now I need support to perform routine experiments, know how to prepare data but not analyze it, and have only read enough literature to start the edges of a jigsaw puzzle.

It's like being a first year again, except now I know how frustratingly limited I am.

Two weeks ago I started a post-doc in Alan Carleton's lab at the University of Geneva, which has entailed completely switching my field.  My background was in cellular neuroscience studying AMPA receptor trafficking and synaptic plasticity in slices.  I am now investigating olfaction (and hopefully taste) using multi-electrode recording and channelrhodopsin in vivo. Where I once had a good handle on the literature of AMPA receptor trafficking, I know only the basics of olfaction.  And while I have done some in vivo electrophysiology before, the details of recording from awake animals and analyzing thousands of spikes of data is daunting.

Before I started my post-doc, I was somewhat aware of my ignorance, and optimistically planned that it would take me 3-6 months to get moderately well trained.  Yet now that I am climbing the learning curve, the slope seems steeper than I anticipated, even while by reasonable standards I am doing just fine.  Maybe it just means I am learning that much more.

One thing I've learned is that no one has any idea what serotonin does (boy am I going to regret typing this when I finally stumble on a paper that explains it). Part of my project involves stimulating serotonergic centers, and measuring how that influences olfactory bulb processing. As a grad student I learned that serotonin is a neuromodulator, and that it's involved in depression and drug addiction (Duke had really great graduate training). So I performed a literature search, and found that all the reviews are from psychiatry journals, and the most cited hard neuroscience review is a 1992 review by Barry Jacobs.  As far as I can tell there has not been a single well-cited neuroscience review focusing on serotonin since Jacobs's thorough, but (hopefully) outdated review.

Getting back to serotonin, it's a fascinatingly ubiquitous molecule. It is involved in a multitude of bodily functions, from bowel movement and vascular dilation, to cognition, motor control and more.  There are fifteen receptor subtypes that are expressed throughout the brain and body, and many targets are directly innervated by different receptor subtypes with diametrically opposing effects.  Neural activity in serotonergic nuclei like the dorsal Raphe is correlated with arousal, and these nuclei are completely silent during REM sleep. Some papers have shown serotonin generally depresses sensory processing, and that Raphe neurons are silent during focused sensation, but it's all rather vague.  Despite all the research on serotonin, there is no obvious neural correlate with its activity, not reward, salience, arousal, attention, decision making, nothing.  Which perhaps is for the best given that it's involved in everything.

I'm not too keen about neuromodulation, but it seems like the field is so wide open that if I discover anything, it would be "significant."

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