CENTRAL SEROTONERGIC PATHWAYS REGULATING ENERGY BALANCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 阐明能量稳态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，在人类和动物研究中已经报道了通过黑皮质素-4受体（MC 4-Rs）在调节能量平衡的代谢、神经内分泌和行为参数中对中枢黑皮质素途径的实质性支持。然而，对CNS MC 4-R表达和调节这些生理和行为效应的途径知之甚少。 神经递质5-羟色胺（5-羟色胺，5-HT）的理想位置有助于中央MC 4-R的行动，基于投射途径和受体表达。 我们有强有力的初步数据表明，大脑5-HT通路调节黑皮质素神经元。 本提案中概述的研究将调查5-HT和特定5-HT受体在与肥胖和II型糖尿病相关的生理和行为过程中调节CNS黑皮质素系统的作用。 我们提供了一系列神经解剖学、药理学、遗传学、生理学、行为学和电生理学实验来测试该模型的组成部分。 我们预计，本提案中概述的研究将有助于更好地了解调节肥胖和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.