Vagus Nerves Provide a Robust Afferent Innervation of the Mucosa Throughout the Body of the Esophagus in the Mouse.

The vagal afferent nerves regulate swallowing and esophageal motor reflexes. However, there are still gaps in the understanding of vagal afferent innervation of the esophageal mucosa. Anatomical studies found that the vagal afferent mucosal innervation is dense in the upper esophageal sphincter area but rare in more distal segments of the esophagus. In contrast, electrophysiological studies concluded that the vagal afferent nerve fibers also densely innervate mucosa in more distal esophagus. We hypothesized that the transfection of vagal afferent neurons with adeno-associated virus vector encoding green fluorescent protein (AAV-GFP) allows to visualize vagal afferent nerve fibers in the esophageal mucosa in the mouse. AAV-GFP was injected into the vagal jugular/nodose ganglia in vivo to sparsely label vagal afferent nerve fibers. The esophageal tissue was harvested 4-6 weeks later, the GFP signal was amplified by immunostaining, and confocal optical sections of the entire esophagi were obtained. We found numerous GFP-labeled fibers in the mucosa throughout the whole body of the esophagus. The GFP-labeled mucosal fibers were located just beneath the epithelium, branched repeatedly, had mostly longitudinal orientation, and terminated abruptly without forming terminal structures. The GFP-labeled mucosal fibers were concentrated in random areas of various sizes in which many fibers could be traced to a single parental axon. We conclude that the vagus nerves provide a robust afferent innervation of the mucosa throughout the whole body of the esophagus in the mouse. Vagal mucosal fibers may contribute to the sensing of intraluminal content and regulation of swallowing and other reflexes.