Neurocircuits that regulate circadian rhythms

项目摘要 虽然调节昼夜节律和能量稳态的系统紧密耦合在一起， 将它们连接在一起的途径尚不清楚。我们最近的研究发现了一种新的， 下丘脑背内侧（DMH）中表达瘦素的神经元亚群的生理作用 受体在摄食、运动活动和相关代谢节律的昼夜节律控制中的作用。的 这项计划的首要目标是确定神经回路的昼夜节律控制DMH 瘦素受体（LepR）神经元和相关的摄食和代谢反应。拟议的目标是：（1） 表征DMH LepR神经元活动的节律性; 2）确定特定的 这些神经元的子集在昼夜节律控制进食行为，代谢和运动，和3）， 鉴定DMH LepR神经元的上游调节物，其调节摄食和代谢的昼夜节律控制。 为了实现这一目标，我们将整合先进的神经科学技术，包括体内纤维光度测定， 病毒追踪和化学遗传学技术，沿着交叉遗传学方法， 综合啮齿动物代谢表型分析。总之，这项工作将从根本上推进我们的知识 的神经回路的基础内源性节律的行为，喂养，和代谢，并可以 预计将促进治疗和预防肥胖及相关疾病的新策略的发展， 人类的疾病。

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.