Dorsomedial Hypothalamic Pathways and Energy Balance

点击翻译按钮获取中文摘要

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