The gastroesophageal junction is characterized by a high pressure zone that is considered to be the major physiological barrier preventing gastroesophageal reflux. Studies indicate that the crural diaphragm and the intrinsic lower esophageal sphincter are important to the genesis of the high pressure zone, and that both muscles act in concert to form the anti-reflux barrier and, during swallowing, relax to permit entry of a bolus into the stomach. The research focuses on the brainstem pathways that mediate the gastrointestinal function of the crural diaphragm. Our hypothesis is that modulation of crural diaphragmatic activity in concert with events at the lower esophageal sphincter is mediated by a central pathway independent of that for its respiratory function. Established neurophysiological and neuroanatomical techniques will be used to investigate the afferent and efferent pathways over which esophageal activity modulates crural diaphragmatic function. The response of medullary inspiratory neurons of the dorsal and ventral respiratory groups, which drive phrenic motor neurons, to esophageal distention will be studied using electrophysiological recording techniques. Using the neural tracer, horseradish peroxidase, the medullary sites of termination of vagal afferents from the esophagus will be determined. To supplement these anatomical studies, the antidromic mapping technique will be used to determine the sites of projection and branching pattern of nodose ganglion neurons, having esophageal receptor endings that respond to stimuli which evoke crural inhibition. Using localized injections of horseradish peroxidase, these descending projections to the C6 phrenic nucleus, which contains neurons innervating the crural diaphragm, will be compared to the projections to the C5 phrenic nucleus. The sites of injection will be controlled electrophysiologically. Knowledge of the connections and behavior of the neural elements modulating the crural diaphragm during gastrointestinal function should help to elucidate the relationship between esophageal and diaphragmatic function in mammals. Thus, these studies may have direct bearing on the future clinical management of swallowing disorders as well as gastroesophageal reflux.
