Evidence for a novel neuronal projection from the esophagus to the airways in guinea pigs

The aim of the study was to characterize calretinin expressing nerve fibers found to be associated with tracheal parasympathetic ganglia in guinea pigs. Retrograde tracing from the trachea with cholera toxin B identified parasympathetic preganglionic neurons in the nucleus ambiguus and dorsal motor nucleus of the vagus nerve, sensory neurons in the nodose, jugular and dorsal root ganglia, and sympathetic postganglionic neurons in the superior cervical and stellate ganglia. Although some calretinin‐expressing neurons were identified in each of these locations, neurons specifically traced from the airways never expressed calretinin. Calretinin‐immunoreactive nerve fibers disappeared from tracheal ganglia following 48 hours in organotypic culture (confirming an extrinsic origin) but persisted when tracheae were co‐cultured with the esophagus intact. A population of esophageal myenteric plexus neurons was immunoreactive for calretinin and co‐expressed acetylcholine but not nitric oxide synthase. Electrical stimulation of the esophagus in vitro evoked contractions of the trachea that were significantly (P<0.05) inhibited by hexamethonium. Taken together, these data suggest that a subset of esophageal neurons, that express calretinin and contain acetylcholine, provide excitatory input to tracheal cholinergic ganglia in guinea pigs.