DESCRIPTION (provided by applicant): A deeper understanding of the biologic origins of obesity will require mapping the neural networks that control feeding. Two key neural populations that control feeding are AgRP and POMC neurons in the hypothalamus. Despite extensive study of these cells over the past 20 years little is known about their natural dynamics in vivo. We have used fiber photometry to record the natural activity of AgRP and POMC neurons in awake behaving mice. Using this approach we have discovered that AgRP and POMC neurons are rapidly (seconds) and dramatically modulated by sensory cues associated with food. This regulation is cell-type-specific, is sensitive to food palatability and nutritional state, and occurs before any food is consumed. These data indicate the existence of an unanticipated neural pathway by which sensory detection of food generates rapid anticipatory changes in the activity of AgRP and POMC neurons. Importantly, this rapid regulation provides a mechanism for AgRP and POMC neurons to integrate sensory and hedonic cues with homeostatic information about nutritional state, suggesting a more complex role for these "first order" neurons than is currently appreciated. We propose here to delineate the neural mechanisms underlying the remarkable rapid regulation of these cells by food detection. We propose further to explore the downstream pathways to which these sensory cues are communicated in order to understand their role within a distributed feeding network.