MEAL-RELATED VAGAL AFFERENT GI SIGNALS

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.