Interrogating brain circuits that control feeding caused by fasting or by craving

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PROJECT ABSTRACT Neuron populations in the hypothalamus form nodes within a larger distributed network to control multiple aspects of feeding behavior in mammals. The goal of this project is to functionally interrogate newly mapped hypothalamic relay circuits that control feeding behavior. We will employ viral-based tract tracing, optogenetics, chemogenetics, behavioral analyses of feeding, wide-field and multifluorescence imaging, and reference atlas- based mapping; to determine whether these relay circuits in the hypothalamus mediate feeding triggered either by an overnight fast or by craving for rewarding foods. We will deposit all mapped and probed brain circuit locations within an online neuroinformatics database. The hypothalamus has remained a relatively uncharted and poorly defined brain structure that is otherwise critical for feeding behavior. Knowledge of the basic circuit organization of this structure, and its functional/behavioral validation, is critical for scientists to be able to further experimentally manipulate selected sub-populations of neurons in this structure to study various aspects of feeding control. This, in turn, is expected to yield novel targets within the brain suitable for designing rationale therapeutics and treatments to help prevent or mitigate the effects of obesity, overeating, and metabolic disorders.