MEAL-RELATED VAGAL AFFERENT GI SIGNALS

这项建议的首要目标是确定与膳食有关的刺激 从胃、小肠和肝脏发出，引起迷走神经 大鼠的传入活动，并确定胃肠道事件如何 与食物摄入量相关的信息可以在 外周传入迷走神经。这些实验的基本基础 解决这些目标的观点是，机械和化学刺激在 食物摄入引起的胃、小肠和肝脏提供 对控制饲喂至关重要的信息。迷走神经是一种 连接胃肠道和中枢神经的主要神经解剖通路 涉及食物摄入量控制的系统站点。在体内使用 电生理技术，我们建议识别和表征 迷走神经传入纤维与胃、小肠和肝脏的感受性 菲尔兹。我们将首先根据这些纤维的种类对它们进行分类 对膨胀和化学刺激的反应性。这 分类将为后续设计的实验提供基础 来研究产生这些信号的机制。用于消肿 敏感纤维，我们将检查这种敏感性与 局部胃肠压力和肌肉张力的变化。vbl.使用 药理学和神经切断技术，我们还将检查 这些信号依赖于外在的交感神经和 副交感神经支配。对于化学敏感纤维，我们将 描述他们敏感性的性质，检查他们对 PH、渗透压和元素常量营养素刺激。我们将表演 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。跟随 识别这些类型的整合，我们将检查神经， 迷走神经传入的神经递质和神经内分泌调节 整合。总之，这些实验将显著推进我们的 与进食有关的迷走神经传入信号的认识 可能在控制食物方面起作用的胃肠道事件 摄入量、胃肠生理和体重调节。

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.