A latent serotonin-1A receptor-gated spinal afferent pathway inhibiting breathing
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429_2015_Article_1155.pdf
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Author(s)
Yang, Liang
Song, Gang
Ning, Yinghui
Poon, Chi-Sang
Date Issued
December 2015
Journal
Brain Structure and Function
Publisher
Springer Berlin Heidelberg
Citation
Yang, Liang et al. “A Latent Serotonin-1A Receptor-Gated Spinal Afferent Pathway Inhibiting Breathing.” Brain Structure and Function 221.8 (2016): 4159–4168.
Version
Author's final manuscript
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-HT[subscript 1A]Rs) 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-HT[subscript 1A]Rs in lumbar spinal cord unequivocally localized the site of 5-HT[subscript 1A]R-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-HT[subscript 1A]R-based treatment of a variety of respiratory abnormalities.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Division of Comparative Medicine
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1007/s00429-015-1155-z
