CENTRAL SEROTONERGIC PATHWAYS REGULATING ENERGY BALANCE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。阐明能量稳态的基本神经生物学对预防肥胖和II型糖尿病至关重要。最近，在人类和动物的研究中，大量的研究支持了黑素皮质素的中枢通路，即黑素皮质素-4受体（melanocortin-4 receptor, MC4-Rs）在调节代谢、神经内分泌和能量平衡的行为参数方面的作用。然而，关于中枢神经系统MC4-R的表达和调节这些生理和行为影响的途径，我们所知相对较少。基于投射通路和受体表达，神经递质5-羟色胺（5-羟色胺，5-HT）被理想地定位于参与中枢MC4-R的活动。我们有强有力的初步数据表明，大脑5-HT通路调节黑素皮质素神经元。本研究将探讨5-羟色胺和特异性5-羟色胺受体在中枢神经系统黑素皮质素系统调节中与肥胖和II型糖尿病相关的生理和行为过程中的作用。我们提供了一系列的神经解剖学、药理学、遗传学、生理学、行为学和电生理学实验来测试这个模型的组成部分。我们期望在本提案中概述的研究将有助于更好地理解调节肥胖和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.