Understanding how neural circuits regulate behavior is a major goal of neuroscience. One of the most mysterious behaviors, sleep, is particularly intriguing. The nematode Caenorhabditis elegans offers unique advantages as a model system, including a compact nervous system and an extensive battery of genetic tools. The goal of the PI is to understand the mechanisms by which serotonin, a major bioamine, regulates C. elegans sleep. Although serotonin was generally shown to antagonize sleep in various animals, understanding how this is done remains a challenge. Thus, the PI will combine novel computational tools, a detailed genetic analysis and state of the art recordings of neuronal activity in freely behaving animals to test the hypothesis that serotonin signaling antagonizes C. elegans sleep through specific pathways. The combination of a simple model system and novel methods is expected to result in identifying specific cells and molecules through which serotonin exerts its functions. A growing body of work shows that the mechanisms that regulate sleep in C. elegans are, at least in part, similar to those in other animals. Thus, sleep may be ancient and simple model animals may be crucial for understanding this complex phenomenon. The proposed research will offer substantial, novel and important insights into the mechanisms that regulate sleep. Elements of the proposed work will be used to involve undergraduate students in research experiences. Emphasis will be given to increasing the participation of women and other underrepresented minority groups and the PI will engage in a spectrum of activities specifically aimed at providing mentorship and opportunities for students from diverse backgrounds. In addition, novel software tools for analyzing behavior on high power computation resources will be made publically available on the public software repository, GitHub (https://github.com).
