CENTRAL SEROTONERGIC PATHWAYS REGULATING ENERGY BALANCE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。阐明能量动态平衡的基本神经生物学对于预防肥胖和II型糖尿病至关重要。最近，通过黑素皮质素-4受体(MC4-Rs)，在调节代谢、神经内分泌和能量平衡的行为参数方面，人类和动物的研究报告了对中枢黑素皮质素途径的实质性支持。然而，对中枢神经系统MC4-R的表达和调控这些生理和行为效应的途径知之甚少。根据投射途径和受体表达，神经递质5-羟色胺(5-羟色胺，5-羟色胺)处于促进中枢MC4-R活动的理想位置。我们有强有力的初步数据表明，大脑5-羟色胺通路调节黑素皮质素神经元。该提案中概述的研究将探讨5-羟色胺和特定的5-羟色胺受体在与肥胖和II型糖尿病相关的生理和行为过程中对中枢黑素皮质素系统的调节作用。我们提供了一系列神经解剖学、药理学、遗传学、生理学、行为学和电生理学的实验来测试这个模型的组件。我们预计，这项提案中概述的研究将有助于更好地了解调节肥胖症和II型糖尿病的复杂神经回路，并可能为治疗提供新的方向。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Elucidating the basic neurobiology of energy homeostasis is paramount in the prevention of obesity and type II diabetes. Recently, substantial support for the central melanocortin pathways, through the melanocortin-4 receptors (MC4-Rs), in the regulation of metabolic, neuroendocrine, and behavioral parameters of energy balance has been reported in human and animal studies. However, relatively little is known about CNS MC4-R expression and pathways modulating these physiological and behavioral effects. The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) is ideally positioned to contribute to the actions of central MC4-R, based on projection pathways and receptor expression. We have strong preliminary data indicating that brain 5-HT pathways regulate melanocortin neurons. The research outlined in this proposal will investigate the role of 5-HT and specific 5-HT receptors in the modulation of the CNS melanocortin system in physiological and behavioral processes associated with obesity and type II diabetes. We offer a seies of neuroanatomical, pharmacological, genetic, physiological, behavioral and electrophysiological experiments to test components of this model. We anticipate that the studies outlined in this proposal will contribute to a better understanding of the complex neural circuitry regulating obesity and type II diabetes and may provide new directions for treatment.