Optical activity recording and serotonergic modulation of C. elegans behavior

Abstract

I propose to study the serotonergic modulation of C. elegans locomotory behavior using optical activity recording and optical stimulation of specific neurons together with pharmacological, molecular and genetic tools. A genetically-encoded voltage sensitive probe will be expressed under specific promoters in sensory and interneurons and used to record neuronal activity. This will enable the identification and characterization a postulated locomotory CPG and permit characterization of network activity under various conditions. A transgenic photostimulation system will be also expressed in specific sensory and interneurons to stimulate them in a noninvasive manner. The effect on the nematode behavior and neuronal activity will elucidate the locomotory network and its functional connectivity. Pharmacological and genetic manipulations will be used to dissect different aspects of the 5-HT modulation of behavior. Lastly, a naturally occurring 5-HT hypersensitivity allele will be cloned. Apart from my 3-month long Grass Fellowship, I had never studied C. elegans, applied molecular techniques nor used activity imaging. This is a good opportunity to fill the molecular and genetic gap in my scientific background. Also, I will be able to take these optical tools for recording and stimulating neuronal activity in C. elegans and use them when I start my own laboratory and share them with colleagues. C. elegans is a very promising neuroethological model. In several years it will probably be the first animal in which all neurons will be recorded at once during natural behavior and behavioral plasticity.