Autonomic Control of Body Weight and Feeding

拟议的项目将继续对进食和身体的神经机制进行有计划的调查。 体重调节该项目的长期目标是提供治疗摄食性疾病所需的信息。 在一些实施方案中，本发明的组合物用于治疗疾病，尤其是肥胖症和多种胃肠（GI）疾病。迷走神经是主要的 连接大脑和胃肠道的神经通路。迷走神经感觉和运动轴突 协调能量稳态的生理学，包括短期和长期控制 摄入量和体重。令人惊讶的是，考虑到迷走神经的至关重要性，许多神经的 结构和功能特征，特别是有关充分了解摄入， 未描述。因此，该项目的直接目标是进行一系列有希望的分析， 描述了迷走神经投射的形态类型、区域分布和功能，迷走神经投射连接着神经系统。 大脑和胃肠道第一个具体目标是表征和映射不同的迷走神经和其他内脏神经。 胃里的感觉末梢第二个具体目标是描述和映射迷走神经和其他神经元。 内脏感觉末梢前两个目标的实验将使用最近改编的 神经示踪剂协议，以提供化学、机械、奥斯莫和热的库存和地图， 第三个目的是表征和映射不同的迷走神经运动投射， 胃肠道这第三个系列的实验将使用示踪剂产生一个清单，并为地图，电机 大脑协调GI功能的投射。最后的目的是评估摄食的变化， 与胃肠道神经支配的选择性结构变化相关的行为。的实验 该目标将在涉及迷走神经横断的动物模型中使用结构-功能相关性， 再生、选择性突变产生的迷走神经丧失以及胃和胃的手术操作 十二指肠。这些目标与开发肥胖症和其他代谢性疾病的治疗方法密切相关， 消化系统疾病拟议的实验将产生一个更充分的神经科学基础， 改进肥胖手术（例如，旁路和起搏器植入物），现在主要通过试验设计， 错误，以及用于治疗进食障碍，反流病， 肠易激综合征、消化性溃疡、自主神经病和内脏痛。

The proposed project continues a programmatic investigation of the neural mechanisms of feeding and body weight regulation. The long-range goal of the project is to provide information needed for treating ingestive disorders, notably obesity, and a variety of gastrointestinal (Gl)diseases. The vagus nerve is the major neural pathway reciprocally connecting the brain and the Gl tract. Vagal sensory and motor axons coordinate much of the physiology of energy homeostasis, including both short-term and long-term controls of ingestion and body weight. Surprisingly, given the crucial importance of the vagus, many of the nerve's structural and functional features particularly relevant to an adequate understanding of ingestion are as yet undescribed. Thus, the immediate goal of the project is to conduct a series of promising analysesthat are characterizing the morphological types, regional distributions, and functions of vagal projections that link the brain and Gl tract. The first specific aim is to characterize and map the different vagal~and other visceral- sensory endings in the stomach. The second specific aim is to describe and map the vagal-and other visceral-sensory endings in the intestines. The experiments of these first two aims will use recently adapted neural tracer protocols to provide inventories of, and maps for, the chemo-, mechano-, osmo-, and thermo- receptors throughout the gut.The third aim is to characterize and map different vagal motor projections to the Gl tract. This third series of experiments will use tracers to yield an inventory of, and maps for,the motor projections by which the brain coordinates Gl functions. The final aim is to evaluate alterations in ingestive behavior associated with selective structural changes in the innervation of the Gl tract. The experiments of this aim will use structure-function correlations in animal models involving vagus nerve transections and regeneration, vagal losses produced by selective mutations, and surgical manipulations of the stomach and duodenum. The aims are critically relevant to developing treatments for obesity and other metabolic and digestive diseases. The proposed experiments will generate a more adequate neuroscience foundation for refining obesity surgeries (e.g., bypasses and pacemaker implants), now designed primarily through trial and error, and other interventions of the Gl tract that are used in the treatment of eating disorders, reflux disease, irritable bowel syndrome, peptic ulcers, autonomic neuropathies, and visceral pain.