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 a comprehensive functional neuroanatomy of energy homeostasis. For the immediate future, the proposed experiments concentrate on a series of structure-function analyses of the vagus nerve. Extensive evidence has established that the vagus, the Xth cranial nerve, is critically involved in controlling ingestion and body energy regulation. Presently, however, continued progress in analyzing vagal mechanisms involved in ingestive behavior and physiology is seriously limited by a lack of fundamental structural information about the vagal projections to the gastrointestinal tract. Hence, the immediate goal of the project is the completion of a series of promising analyses that are characterizing the morphological types, regional topographies and functions of vagal projections linking the brain and GI tract. The first aim is to complete a series of experiments on vagal afferent, or sensory, endings in the alimentary canal. This aim includes characterizing structurally and then classifying afferent terminals in the mucosa and submucosa of the GI tract. It also includes developing topographic maps of the concentrations of these chemo-, osmo-, thermo- and mechano- receptors throughout the GI tract. The second aim is to characterize the patterns and timetables of regeneration of each of the different types of vagal projections to the GI tract. These experiments will also correlate the newly identified patterns of structural plasticity with recovery of function. The third aim is to extend our structure-function analyses by screening mutant mice with selective afferent vagal ablations for potential alterations in feeding behavior. Inventories of the different vagal endings, surveys of their terminal distributions, and characterizations of the plasticity in these vagal projections produced by damage or mutation will yield information needed to design, guide and interpret both experimental and surgical manipulations of the autonomic nervous system and GI tract. The program outlined also will extend our understanding of major neural mechanisms implicated in metabolic and digestive diseases including obesity, eating disorders, anorexia, disorders of swallowing, diabetes, vagal dysfunction, autonomic neuropathies, visceral pain, irritable bowel syndrome, and peptic ulcers.