This proposal contains new experiments to study the central and peripheral neural controls of colonic motility and defecation. Three extrinsic neural control systems will be studied. I. Sacral parasympathetic pathway. In vitro morphological (dye injection of neurons) electrophysiological pharmacological techniques and measurements of in vitro smooth muscle mechanical activity will be used. Studied with these techniques will be directed at central questions of: a) intrinsic neural factors which regulate the output from parasympathetic colonic neurons, b) morphological properties of parasympathetic neurons, c) effect of central preganglionic fibers and intrinsic gastrointestinal fibers on the spontaneous mechanical activity of smooth muscle, and d) the effect of polypeptides on synaptic transmission and electrophysiological properties of neurons in parasympathetic colonic ganglia and on the smooth muscle of the colon and rectum. II. Lumbar sympathetic pathway. In vitro morphological (dye injection, horseradish peroxidase technique), electrophysiological, pharmacological measurements and in situ measurements of colonic and urinary bladder motility will be used to determine the function and organization of postganglionic sympathetic neurons in lumbar sympathetic chain ganglia. Studies with these techniques will be directed to a) establishing the electrophysiological properties, synaptic transmission, responsiveness to polypeptides, and morphological characteristics of postganglionic sympathetic neurons which project to the abdominal viscera and b) determine the effects of the visceral postganglionic neurons on the smooth muscle of the colon and urinary bladder. III. Sacral motor pathway to the external anal sphincter. In situ electrophysiological, electromyographic and force measurements will be used to measure a) the contractile properties of the skeletal muscle fibers of the external anal sphincter and b) the smooth muscle of the rectum, internal anal sphincter and anal canal region.
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