Peptidergic neuromodulation of microcircuits that control chemosensation-induced behaviors

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PROJECT SUMMARY One of central functions of neuromodulation is to adjust the internal representations of sensory information ac- cording to the internal states of an individual. In particular, chemosensation can have dramatically different bio- logical meanings depending on the nutritional state. For instance, the smell of food not only informs an animal where the food is, but also how valuable it is. According to nutritional need, an animal uses the perceived value of the food as a context to adjust the level of competition with other conspecifics. While hunger is known to change the detection thresholds of olfactory and gustatory sensory neurons through neuromodulation, how the nervous system uses chemosensory cues as contextual information for social behaviors remains largely un- known. The long-term goal of this research program is to characterize the neuropeptidergic modulation of chemosensory circuits by deconstructing this physiological process into clearly defined, behaviorally relevant molecular and neuronal events. The fruit fly Drosophila melanogaster is ideal for achieving this goal. As a ge- netically tractable model organism, the fly allows precise control of neuronal populations with defined behav- ioral functions and genes involved in neuromodulation. During the previous funding period, the functions of tachyninergic neuromodulatory microcircuits that control aggressive behavior were comprehensively character- ized at the molecular and circuit levels. Building upon our expertise with Drosophila genetics and social behav- ior, the proposed project will characterize how the fly nervous system uses peptidergic neuromodulation to transform a food-derived odor into a cue to adjust the level of aggression. The three specific aims, each sup- ported by successful preliminary studies, are to: (1) characterize neuropeptidergic cells that convert protein deficit into altered representations of chemical stimuli, (2) characterize molecular and circuit mechanisms of hugin neuromodulation, and (3) determine specific chemosensory pathways that mediate food-odor-driven ag- gression. In Aim 1, the neuropeptide-releasing cells that mediate the promotion of aggressive behavior in pro- tein-deprived flies will be identified, and their function for encoding the nutritional state will be behaviorally characterized. In Aim 2, functions of neuropeptides and their cognate receptors in the midgut and in the brain will be characterized through genetic, physiological, and behavioral approaches. In Aim 3, the specific class of olfactory sensory neurons that detect key volatile compounds emitted from yeast, and the neural node in the olfactory pathway that are modulated by above-mentioned neuropeptides, will be characterized. The results from the proposed experiments will uncover the fundamental role of peptidergic neuromodulation in transform- ing olfactory information into a behaviorally important environmental context. Neuromodulation is important for encoding the hunger state across animal species, and many neuropeptides involved in hunger control are evo- lutionarily conserved. Knowledge obtained through this project may lead to a better understanding of the neural basis of hunger-dependent changes in olfactory perception in humans.