Project Summary While the systems that regulate circadian rhythms and energy homeostasis are tightly coupled together, the pathways which connect them together are not well understood. Our recent findings have identified a novel, physiological role for a subset of neurons in the dorsomedial hypothalamus (DMH) that express the leptin receptor in the circadian control of feeding, locomotor activity and associated metabolic rhythms. The overarching goal of this proposal is to identify the neurocircuitry linking circadian rhythms to control of DMH leptin receptor (LepR) neurons and associated feeding and metabolic responses. Proposed aims seek to 1) characterize the rhythmicity of DMH LepR neuronal activity; 2) identify the contribution made by specific subsets of these neurons in the circadian control of feeding behavior, metabolism and locomotion, and 3) to identify upstream regulators of DMH LepR neurons that regulate circadian control of feeding and metabolism. To accomplish this, we will integrate advanced neuroscience techniques including in vivo fiber photometry, viral track tracing and chemogenetic techniques, along with an intersectional genetics approach and comprehensive rodent metabolic phenotyping. Together, this work will fundamentally advance our knowledge of the neural circuits underlying endogenous rhythms of behavior, feeding, and metabolism and can be expected to facilitate the development of new strategies for the treatment and prevention of obesity and related disorders in humans.