Medical Research

Salk Institute

Sreekanth Chalasani, James Fitzpatrick
La Jolla, CA
$1,000,000
June 2013

A central challenge of modern neuroscience is to decode how an organism responds to external threats, particularly how neural circuits elicit appropriate behaviors. Neural circuits, including those in humans, are optimized to detect and trigger avoidance of threats in the environment, but most of the basic underlying molecular machinery, including synaptic signaling, is poorly understood. Complete understanding of these circuits requires classification of all participating neurons, their connections and their interactions with other systems (including sympathetic connections in the gut, circulation, musculature, etc.). However, this level of analysis is nearly impossible to achieve in a complex vertebrate system. One unconventional, yet rational approach to understand these behaviors is to dissect the relevant neural circuits in a simpler, more tractable model, Caenorhabditis elegans. The team has developed a novel model of threat behaviors using the interactions between C. elegans and a second nematode, an aggressor Pristionchus pacificus. This proposal will dissect the molecular signaling pathways that integrate external threats into behavioral and physiological responses using a combination of genetics, behavioral analysis, pharmacology, and advanced imaging methods. Findings from these analyses of threat-activated networks will provide significant insights into the nature of similar behaviors across species.

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