MEAL-RELATED VAGAL AFFERENT GI SIGNALS

这项建议的首要目的是确定与膳食有关的刺激 来自胃、小肠和肝脏， 传入活动在大鼠，并确定如何胃肠道事件 与食物摄入量相关的可能会在 外周迷走传入神经 实验的基础是 解决这些目标的观点是，机械和化学刺激， 由食物摄入引起的胃、小肠和肝脏提供 对控制进食至关重要的信息。 迷走神经是 连接胃肠和中枢神经的主要神经解剖通路 控制食物摄入的系统站点。使用体内 电生理技术，我们建议识别和表征 胃、小肠和肝的迷走神经传入纤维 领域的 我们将开始根据它们的特性对这些纤维进行分类。 对膨胀和化学刺激的反应。 这 分类将为后续实验设计提供基础 研究产生这些信号的机制。 用于膨胀 敏感纤维，我们将研究这种敏感性的关系， 局部胃肠道压力和肌肉张力的变化。 使用 药理学和神经切断技术，我们还将研究 这些信号对外在交感神经和 副交感神经支配 对于化学敏感纤维，我们将 描述他们的敏感性的性质，检查他们的反应， pH、渗透压和元素常量营养素刺激。 我们将执行 评估这些迷走神经传入整合程度的实验 来自多个胃肠道和肝脏部位的刺激。 以下 识别这些类型的整合，我们将研究神经， 迷走神经传入的神经递质和神经内分泌调节 一体化总之，这些实验将大大推进我们的 对饮食相关的迷走神经传入信号的理解 可能在控制食物中发挥作用的胃肠道事件 在胃肠道生理学和体重调节中。

The overriding aim of this proposal is to identify meal-related stimuli arising from the stomach, small intestine and liver that elicit vagal afferent activity in the rat, and to determine how gastrointestinal events associated with food intake may be integrated at the level of the peripheral afferent vagus. The underlying basis of the experiments addressing these aims is the view that mechanical and chemical stimuli in the stomach, small intestine and liver provoked by food intake provide information critical to the control of feeding. The vagus nerve is a major neuroanatomical pathway linking gastrointestinal and central nervous system sites involved in food intake control. Using in vivo electrophysiological techniques, we propose to identify and characterize vagal afferent fibers with gastric, small intestinal and hepatic receptive fields. We will begin by classifying these fibers according to their responsiveness to distension and chemical stimulation. This classification will provide the basis for subsequent experiments designed to examine the mechanisms giving rise to these signals. For distension sensitive fibers, we will examine the relationship of this sensitivity to changes in local gastrointestinal pressure and muscle tension. Using pharmacological and neural disconnection techniques, we will also examine the dependence of these signals on extrinsic sympathetic and parasympathetic innervation. For chemosensitive fibers, we will characterize the nature of their sensitivity, examining their responses to pH, osmolarity, and elemental macronutrient stimuli. We will perform experiments evaluating the extent to which these vagal afferents integrate stimulation from multiple gastrointestinal and hepatic sites. Following identification of these types of integration, we will examine the neural, neurotransmitter and neuroendocrine mediation of this vagal afferent integration. Together, these experiments will significantly advance our understanding of vagal afferent signals elicited by meal-related gastrointestinal events that may play a role in the control of food intake, in gastrointestinal physiology and in body weight regulation.