Dorsomedial Hypothalamic Pathways and Energy Balance

描述（由申请人提供）：下丘脑在维持能量稳态中起核心作用。从早期的电刺激或损伤研究到现代的神经回路分析，各种下丘脑核，包括弓状核（ARC）、下丘脑腹侧侧核（VMH）、室旁核（PVN）和下丘脑外侧区（LH），在控制食物摄入和能量平衡中的作用已经得到了很好的证明。相比之下，下丘脑背内侧核（DMH）在调节摄食和体重中的作用尚不完全清楚。尽管DMH病变已被证明会影响食物摄入、体重和线性生长，但这些病变效应背后的神经回路或该核对整体能量稳态的基本贡献才刚刚开始被解开。最近的一些研究结果表明，DMH含有多种与摄食有关的神经肽和肽受体，但这些系统之间可能有助于摄食控制的潜在相互作用尚未确定。

DESCRIPTION (provided by applicant): The hypothalamus plays a central role in maintaining energy homeostasis. From early electrical stimulation or lesion studies to modern neuronal circuitry analyses, roles for various hypothalamic nuclei, including the arcuate nucleus (ARC), ventralmedial hypothalamus (VMH), paraventricular nucleus (PVN) and the lateral hypothalamic area (LH), in the control of food intake and energy balance are well documented. In contrast, the actions of the dorsomedial hypothalamic nucleus (DMH) in regulating feeding and body weight are incompletely understood. Although DMH lesions have been demonstrated to affect food intake, body weight and linear growth, the neural circuitry underlying these lesion effects or the basic contributions of this nucleus to overall energy homeostasis are only beginning to be unraveled. A number of recent findings suggest that the DMH contains multiple feeding related neuropeptides and peptide receptors but the potential interactions among these systems that could contribute to feeding control have not been identified. The proposed experiments will focus on leptin, Neuropeptide Y (NPY), melanocortin, corticotropin-releasing factor (CRF) and cholecystokinin (CCK) systems, and assess their possible interactions within the DMH in energy balance. To provide a basis for potential interactions among these peptide systems, I will use double labeled in situ hybridization histochemistry or immunohistochemistry or combinations of both to characterize DMH neurons and their histochemical relationships. After this neuroanatomical characterization, I will assess patterns of DMH gene expression in response to a number of treatments that alter energy demands to identify the functional significance of these DMH peptide systems in energy control. Together, these neurochemical and functional demonstrations will provide a clear view of the role of the DMH in energy balance