CONTROL OF FEEDING BEHAVIOR--HEPATIC AFFERENT SIGNALING

说明(改编自应用程序) 拟议研究的总体目标是确定属性 控制摄食行为的从肝脏到大脑的神经通路 和能量平衡。该项目将确定肝脏代谢的刺激因素 激活迷走神经传入纤维和脑干神经元。在职业生涯中 获奖后，候选人将学习用于记录的神经生理学技术 麻醉大鼠的神经系统；这种训练将促进 候选人的职业目标是成为一名独立研究科学家。加里博士 康奈尔大学的施瓦茨将提供迷走神经录音方面的培训 传入神经活动；教学将重点放在分离单个 迷走神经肝支的单位和刺激。拉尔夫·诺格伦博士 宾夕法尼亚州立大学将培训考生录制单人单位 来自孤束核(NTS；脑干感觉中继核 对于迷走神经)。实验将在莫内尔化学感官中心进行 中心(宾夕法尼亚州费城)与代谢专家马克·弗里德曼博士 控制食物摄入量，作为首要导师。先前的研究表明， 迷走神经是肝脏发出的信号的通道。 新陈代谢影响进食。2，5-脱水-D-甘露醇(2，5-AM)和 巯基乙酸酯(MA)是两种具有不同作用的代谢抑制剂 刺激进食行为。这些代谢抑制剂对血管紧张素转换酶的影响 迷走神经切断术阻止了摄食，这表明 这些抑制剂在进食时。在当前项目中，2，5-AM和MA将 门静脉输注以隔离肝脏的治疗，而 电生理记录来自迷走神经和NTS。这个 2，5-AM和MA对单个单位传入活动的影响将与 确定这些治疗是否激活了相同数量的肝传入 纤维(如果这一群体与葡萄糖敏感型纤维不同)。一个 门静脉上游输注与邻近肝脏输注的比较 将确定2，5-AM和MA的作用部位。论迷失 传入活动。这个项目的结果可能有助于更好地 对神经系统感知的代谢刺激的理解，以及 可能会阐明与肥胖、厌食症和 糖尿病。

DESCRIPTION (adapted from the application) The overall objective of the proposed research is to determine the properties of neural pathways from the liver to the brain that control feeding behavior and energy balance. This project will determine the hepatic metabolic stimuli that activate vagal afferent fibers and brainstem neurons. During the career award, the candidate will learn neurophysiological techniques to record from the nervous system of the anesthetized rat; this training will advance the candidate's career goal to become an independent research scientist. Dr. Gary Schwartz, Cornell University, will provide training in the recording of vagal afferent nerve activity; the instruction will focus on the isolation of single units and stimulation of the hepatic branch of the vagus. Dr. Ralph Norgren, Pennsylvania State University, will train the candidate to record single units from the nucleus of the solitary tract (NTS; brainstem sensory relay nucleus for the vagus). Experiments will be conducted at the Monell Chemical Senses Center (Philadelphia, PA) with Dr. Mark Friedman, an expert in the metabolic control of food intake, as the primary mentor. Previous research indicates that the vagus nerve is the route of passage for signals that arise from liver metabolism to affect feeding. 2,5-anhydro-D-mannitol (2,5-AM) and mercaptoacetate (MA), are two metabolic inhibitors with different actions that stimulate feeding behavior. The effects of these metabolic inhibitors on feeding are blocked by vagotomy, which suggests a peripheral site of action for these inhibitors on feeding. In the current project 2,5-AM and MA will be infused into the portal vein to isolate the treatments to the liver, while electrophysiological recordings are done from the vagus nerve and the NTS. The effects of 2,5-A.M and MA on single unit afferent activity will be compared to determine if these treatments activate the same population of hepatic afferent fibers (and if this population is distinct from glucose-sensitive fibers). A comparison between up-stream portal vein infusion and adjacent liver infusion will determine the site of action for the effects of 2,5 -AM and MA. on vagal afferent activity. Results from this project may contribute to a better understanding of metabolic stimuli that are sensed by the nervous system, and may elucidate neural controls that are involved in obesity, anorexia, and diabetes.