Neural circuits in swallowing and abdominal vagal afferent-mediated lower esophageal sphincter relaxation

Abstract

The purpose of this review is to identify the medullary subnuclei that house neural circuits for lower esophageal sphincter (LES) relaxation. LES relaxation may occur as a component of primary peristalsis elicited by superior laryngeal nerve (SLN) afferent stimulation, secondary peristalsis elicited by esophageal distention or as a component of belch reflex, and transient LES relaxation elicited by gastric vagal afferent stimulation. In mice, SLN stimulation at 10 Hz elicited complete swallowing reflex, including pharyngeal and esophageal peristalsis, and LES relaxation. SLN stimulation at 5 Hz elicited pharyngeal contractions and isolated LES relaxation, which is not accompanied by esophageal peristalsis. Electric stimulation of afferents in the ventral branch of the subdiaphragmatic vagus (vSDV) at 10 Hz also elicited isolated LES relaxation. Using these defined stimuli, c- fos expression was examined in the entire craniocaudal extent of the medullary nuclei. SLN stimulation at 10 Hz induced c- fos expression in neurons in: (1) interstitial (SolI), intermediate (SolIM), central (SolCe), occasional medial (SolM), and dorsomedial (SolDM) solitary subnuclei; (2) motor neurons in the nucleus ambiguus, including its semicompact (NAsc), loose (NAl), and compact (NAc) formations; and (3) dorsal motor nucleus of vagus, including its rostral (DMVr) and caudal (DMVc) parts. The activated neurons represent neurons involved with afferent SLN-mediated reflexes, including swallowing. SLN stimulation at 5 Hz evoked c- fos expression in neurons in SolI, SolIM, SolM, and SolDM but not in SolCe; and motor neurons in NAsc, NAl, and DMVc but not in NAc or DMVr. Stimulation of vSDV induced c- fos expression in neurons in SolM and SolDM and in motoneurons in DMVc. When considered with published reports in other animal species, these data support the speculation that (1) swallow-evoked primary peristalsis involves the following neural circuits: SolI/SolIM → NAsc/NAl for pharyngeal and SolCe → NAc for esophageal (striated muscle) peristalsis, SolM/SolDM → preganglionic neurons in DMVc and DMVr and nitrergic and cholinergic neurons in myenteric plexus for esophageal (smooth muscle) peristalsis, and SolM/SolDM → preganglionic neurons in DMVc → postganglionic nitrergic neurons in the myenteric plexus for LES relaxation; and (2) abdominal vagus-stimulated isolated LES relaxation may involve neurons in SolM and SolDM → preganglionic motor neurons in DMVc → postganglionic nitrergic neurons in the myenteric plexus.