A program is proposed for continuation of study of the neurophysiology of the enteric nervous system and for investigation of the mechanisms by which the intrinsic nervous system of the gut participates in the control and integration of the functions of gastrointestinal effector systems. The objectives of the project are: (1) to compare the electrophysiological properties, synaptic behavior, and morphology of enteric ganglion cells with the behavior of the effector systems in the specialized regions along the alimentary canal; (2) to investigate the neurophysiological mechanisms by which information in efferent fibers of the vagal nerves is interfaced with the integrative circuitry of the enteric nervous system; (3) to investigate mechanisms of processing of sensory information in the enteric nervous system; (4) to compare neuro-effector function in the large intestine of mice with hereditary aganglionic megacolon with neuro-effector function in mice with normal innervation of the bowel; (5) to analyze plasticity and propensity for compensatory adjustment of function within the enteric nervous system after surgical perturbations of the alimentary canal; (6) to continue to exploit the enteric nervous system as a model for analysis of synaptic interactions, information processing, and motor pattern generation by small ensembles of mammalian neurons that for investigative purposes are more accessible than the central nervous system; (7) to elucidate the etiology and pathophysiology of Hirschsprung's disease and related disorders that are associated with malformation and malfunction of the enteric nervous system.
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