title: Sensory and motor innervation of the crural diaphragm by the vagus nerves.
abstract: OBJECTIVE
  During gastroesophageal reflux, transient lower esophageal sphincter relaxation and crural diaphragm (CD) inhibition occur concomitantly. Modifying vagus nerve control of transient lower esophageal sphincter relaxation is a major focus of development of therapeutics for gastroesophageal reflux disease, but neural mechanisms that coordinate the CD are poorly understood.
  
  
  METHODS
  Nerve tracing and immunolabeling were used to assess innervation of the diaphragm and lower esophageal sphincter in ferrets. Mechanosensory responses of vagal afferents in the CD and electromyography responses of the CD were recorded in novel in vitro preparations and in vivo.
  
  
  RESULTS
  Retrograde tracing revealed a unique population of vagal CD sensory neurons in nodose ganglia and CD motor neurons in brainstem vagal nuclei. Anterograde tracing revealed specialized vagal endings in the CD and phrenoesophageal ligament-sites of vagal afferent mechanosensitivity recorded in vitro. Spontaneous electromyography activity persisted in the CD following bilateral phrenicotomy in vivo, while vagus nerve stimulation evoked electromyography responses in the CD in vitro and in vivo.
  
  
  CONCLUSIONS
  We conclude that vagal sensory and motor neurons functionally innervate the CD and phrenoesophageal ligament. CD vagal afferents show mechanosensitivity to distortion of the gastroesophageal junction, while vagal motor neurons innervate both CD and distal esophagus and may represent a common substrate for motor control of the reflux barrier.
authors.affiliation: Nerve-Gut Research Laboratory, Hanson Institute, Frome Road, Adelaide, South Australia 5000, Australia. richard.young@adelaide.edu.au
authors.forename: Richard L
authors.initials: RL
authors.lastname: Young
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Page
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Cooper
authors.forename: Claudine L
authors.initials: CL
authors.lastname: Frisby
authors.forename: L Ashley
authors.initials: LA
authors.lastname: Blackshaw
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D003714:Denervation; D003964:Diaphragm / Q000294:innervation*; D004576:Electromyography; D049630:Esophageal Sphincter, Lower / Q000294:innervation*; D005260:Female; D005289:Ferrets; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D040542:Mechanotransduction, Cellular; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D009433:Neural Inhibition; D056347:Neuroanatomical Tract-Tracing Techniques; D009620:Nodose Ganglion / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology / Q000601:surgery; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D012684:Sensory Thresholds; D013997:Time Factors; D014630:Vagus Nerve / Q000378:metabolism / Q000502:physiology*