The proposed project is designed to provide insight into the neurophysiological relationships between hypothalamic and limbic activity and vagal control over gastric function which are important to an understanding, and eventual management, of stress-induced gastric pathology. It addresses recent findings which indicate that messenger peptides localized in the pre-vagal forebrain nuclei (paraventricular neuleus of the hypothalamus (PVN); bed nucleus of the stria terminalis (BNST); and the central nucleus of the amygdala (CNA) and medullary vagal neurons either exacerbate or suppress the development of stress-induced gastric ulcers. The overall objective of this project is to determine whether neuropeptides which profoundly affect gastrointestinal function, when injected into the brain, do so by acting within a system of forebrain neurons connected directly with second-order neurons in sensory pathways from the stomach and the medullary neurons that project to the stomach. Specifically, the effects of neural activity in the PVN, CNA, and BNST on gastric vagal neurons will be examind using electrical or glutamate microstimulation in conjunction with electro-physiological recording and spike-triggered averaging techniques. Peptides known to be localized within these hypothalamic nuclei, as well as antagonists, will be microinjected into the brain. We will evaluate the peptidergic receptors involved in the hypothalamo-vagal pathway. Gastric motor function will be monitored with extraluminal strain gauges or gastric acid secretion will be measured in order to determine the effect of central nervous system manipulations.
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