The objective of our proposed research is to learn how the central nervous system (CNS) controls gastrointestinal (G.I.) function in the cat. Our objective will be carried out by determining: (1) the origin of the cholinergic neurons innervating the gastrointestinal tract by using retrograde neuroanatomical tracing techniques, (2) the effect of electrically or chemically stimulating CSN sites (as located by the retrograde tracing studies) on G.I. function, (3) the neurotransmitters present at CNS sites deemed important from results obtained by pursuing studies (1) and (2), (4) the afferent projections to CNS sites defined by pursuing studies (1) and (2), (5) the neurotransmitters present in these afferent projections, and (6) the role of the neurotransmitters defined by pursuing studies (3) and (5). Methods to be used include measuring G.I. motility with strain gage transducers and gastric acid and pepsin secretion, retrograde neuroanatomical mapping, immunohistochemical techniques in combination with retrograde tracing techniques, electrical and chemical stimulation of specific CNS sites, and microinjection of putative neurotransmitters (e.g., oxytocin, GABA, TRH, neurotensin, substance P, gastrin, etc.) and antagonists to these neurotransmitters. The results obtained from these studies should provide new insight into: (1) neural determinants of gastric secretion which might evolve as causative factors for either peptic disease or disease characterized by diminished acid secretion, and (2) neural determinants of intestinal motility which might evolve causative factors for irritable bowel syndrome. The results obtained should also pinpoint potential sites where drugs can act through the nervous system to correct derangements in gastrointestinal function.
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