Neural and molecular mechanisms of microbe-sensing in the control of animal behavior - Resubmission - 1

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Project Summary Animals use chemosensation to evaluate their environment and instruct a wide range of behaviors. Chemosensation is used to locate food and mates and to avoid threats. Such chemosensory stimuli are often complex blends of molecules. How information encoded by the multiple chemosensory neurons that sense these cues is integrated to form a representation of the environment and inform behavior is poorly understood. The microscopic roundworm C. elegans is an excellent model to study in order to determine how animals decode complex chemosensory stimuli to instruct behavior. Its simple and stereotyped behaviors are robustly regulated by chemosensory cues from its environment. Importantly, powerful genetic tools and optical methods are available to study the circuits that process chemosensory stimuli. This project will focus on how C. elegans uses its chemosensory system to distinguish nutritive from pathogenic bacteria. C. elegans eats microbes, but it is also susceptible to infection by pathogens. It is, therefore, critical that C. elegans rapidly detect and avoid pathogens, and recent studies indicate that this is accomplished by chemosensation. Previous experiments used an optical method to identify neurons that are differentially activated by nutritive and pathogenic bacteria, and these studies will be extended by determining (1) how the sensation of these microbes generates different patterns of neural activity and (2) how these patterns of neural activity generate distinct foraging behaviors. This project will be conducted at the New York University School of Medicine and will aid in preparing the applicant for a career as an independent researcher. The applicant will engage in professional development activities such as mentoring, teaching, and grant-writing workshops. They will also present this work at institutional and international conferences on a regular basis. Together, these studies will determine mechanisms by which complex chemosensory stimuli are processed. In addition to advancing understanding of a fundamental process in sensation, these studies will also impact how we understand defects of chemosensory processing that underlie human diseases, e.g. sensory processing disorder, eating disorders such as obesity associated with a failure to sense appetitive cues and sensory deficiencies that cause loss of chemesthesis.