title: A latent serotonin-1A receptor-gated spinal afferent pathway inhibiting breathing.
abstract: Spinal afferents such as nociceptive afferents and group III-IV muscle afferents are known to exert an acute excitatory effect on breathing when activated. Here, we report the surprising existence of latent spinal afferents which exerted tonic inhibitory influence on breathing subliminally in anesthetized rats, an effect which was reversed upon activation of serotonin-1A receptors (5-HT1ARs) in lumbar spinal cord, lesion of pontine lateral parabrachial nucleus or suppression of the adjacent Kölliker-Fuse nucleus with NMDA receptor blockade. Small-interfering RNA knockdown of 5-HT1ARs in lumbar spinal cord unequivocally localized the site of 5-HT1AR-mediated gating of these respiratory-inhibiting interoceptive afferents to relay neurons in the spinal superficial dorsal horn at the lumbar level and not cervical spinal or supraspinal levels. Our results reveal a novel somatosensory/viscerosensory mechanism which exerts tonic inhibitory influence on homeostatic regulation of breathing independent from the classical chemoreflex excitatory pathways, and suggest a hitherto unrecognized therapeutic target in spinal dorsal horn for 5-HT1AR-based treatment of a variety of respiratory abnormalities.
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Bldg E25-250, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Bldg E25-250, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Song
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Bldg E25-250, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Bldg E25-250, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. cpoon@mit.edu.
authors.forename: Chi-Sang
authors.initials: CS
authors.lastname: Poon
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D008161:Lumbosacral Region; D008297:Male; D065823:Parabrachial Nucleus / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000502:physiology
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin
keywords: 5-HT1AR; Pontine; Respiration; Spinal cord; siRNA