title: Brainstem sites controlling the lower esophageal sphincter and crural diaphragm in the ferret: a neuroanatomical study.
abstract: The lower esophageal sphincter (LES) and the crural diaphragm (CD) surrounding the esophagogastric junction are key components of the gastroesophageal reflex mechanism, which engages the vago-vagal brainstem circuitry. Although both components work in conjunction to prevent gastroesophageal reflux, little is known about the brain area(s) where this integration takes place. The aims of this study were to: (1) trace the brainstem circuitry associated with the CD and the LES, and (2) determine possible sites of convergence. Experiments were done in adult male ferrets. Under isoflurane anesthesia, recombinant strains of the transneuronal pseudorabies virus (PRV-151 or PRV-Bablu) or the monosynaptic retrograde tracer cholera toxin beta-subunit (CTb) were injected into either the CD or the LES. Following a survival period of 5-7 days, animals were euthanized, perfused and their brains removed for dual-labeling immunofluorescence processing. In animals injected with recombinants of PRV into the CD and the LES, distinct labeling was found in various brainstem nuclei including: area postrema, DMV, nucleus tractus solitarius (NTS), medial reticular formation (MRF) and nucleus ambiguous (NA). Double-labeled cells were only evident in the DMV, NTS and MRF. Injections of CTb into the CD or the LES resulted in retrograde labeling only in the DMV. These findings demonstrate the presence of a direct projection from the DMV to the CD. They further suggest that the neuronal connections responsible for CD or LES function are contained in circuitries that, though largely independent, may converge at the level of DMV, NTS and MRF.
authors.affiliation: Departments of Pharmacology, Georgetown University Medical Center, Washington, DC, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Niedringhaus
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Jackson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pearson
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dretchen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gillis
authors.forename: Niaz
authors.initials: N
authors.lastname: Sahibzada
mesh_terms: D000818:Animals; D031608:Area Postrema / Q000033:anatomy & histology / Q000502:physiology; D001931:Brain Mapping; D001933:Brain Stem / Q000033:anatomy & histology* / Q000502:physiology; D002772:Cholera Toxin; D003964:Diaphragm / Q000294:innervation* / Q000502:physiology; D049630:Esophageal Sphincter, Lower / Q000294:innervation* / Q000502:physiology; D004943:Esophagogastric Junction / Q000294:innervation / Q000502:physiology; D005289:Ferrets / Q000033:anatomy & histology* / Q000502:physiology; D005764:Gastroesophageal Reflux / Q000503:physiopathology; D011558:Herpesvirus 1, Suid; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000502:physiology; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D012154:Reticular Formation / Q000033:anatomy & histology / Q000502:physiology; D017552:Solitary Nucleus / Q000033:anatomy & histology / Q000502:physiology; D013045:Species Specificity; D013194:Staining and Labeling; D014630:Vagus Nerve / Q000033:anatomy & histology* / Q000502:physiology; D017833:Visceral Afferents / Q000033:anatomy & histology* / Q000502:physiology
chemical_list: D002772:Cholera Toxin