Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity

Andrea E Corcoran; George B Richerson; Michael B Harris

doi:10.1152/jn.00870.2013

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Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity

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Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity

Andrea E Corcoran, George B Richerson and Michael B Harris

Journal of neurophysiology, Vol.114(1), pp.381-389

07/2015

DOI: 10.1152/jn.00870.2013

PMCID: PMC4507970

PMID: 25878157

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Abstract

Serotonin (5-HT)-synthesizing neurons of the medullary raphe are putative central chemoreceptors, proposed to be one of potentially multiple brain stem chemosensitive cell types and loci interacting to produce the respiratory chemoreflex. Hypocretin-synthesizing neurons of the lateral hypothalamus are important contributors to arousal state, thermoregulation, and feeding behavior and are also reportedly involved in the hypercapnic ventilatory response. Recently, a functional interaction was found between the hypocretin system and 5-HT neurons of the dorsal raphe. The validity and potential significance of hypocretin modulation of medullary raphe 5-HT neurons, however, is unknown. As such, the purpose of this study was to explore functional interactions between the hypocretin system and 5-HT system of the medullary raphe on baseline respiratory output and central chemosensitivity. To explore such interactions, we used the neonatal in vitro medullary slice preparation derived from wild-type (WT) mice (normal 5-HT function) and a knockout strain lacking all central 5-HT neurons (Lmx1b(f/f/p) mice). We examined effects of acidosis, hypocretin-1, a hypocretin receptor antagonist (SB-408124), and the effect of the antagonist on the response to acidosis. We confirmed the critical role of 5-HT neurons in central chemosensitivity given that the increased hypoglossal burst frequency with acidosis, characteristic of WT mice, was absent in preparations derived from Lmx1b(f/f/p) mice. We also found that hypocretin facilitated baseline neural ventilatory output in part through 5-HT neurons. Although the impact of hypocretin on 5-HT neuronal sensitivity to acidosis is still unclear, hypocretins did appear to mediate the burst duration response to acidosis via serotonergic mechanisms.

Hypoglossal Nerve - physiology

Orexin Receptors - metabolism

Serotonergic Neurons - physiology

LIM-Homeodomain Proteins - metabolism

Orexins - metabolism

Serotonergic Neurons - drug effects

Medulla Oblongata - drug effects

Tissue Culture Techniques

Transcription Factors - genetics

Mice, Knockout

Action Potentials - physiology

Transcription Factors - metabolism

Hypoglossal Nerve - drug effects

LIM-Homeodomain Proteins - genetics

Animals

Orexin Receptor Antagonists - pharmacology

Respiration - drug effects

Serotonin - metabolism

Acidosis - physiopathology

Phenylurea Compounds - pharmacology

Hypoglossal Nerve - physiopathology

Medulla Oblongata - physiology

Action Potentials - drug effects

Hydrogen-Ion Concentration

Details

Title: Subtitle: Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity
Creators: Andrea E Corcoran - Department of Biology and Wildlife, and Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska; Departments of Neurology and Cellular & Molecular Physiology, Yale University, New Haven, Connecticut; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; andrea.e.corcoran@dartmouth.edu
George B Richerson - Departments of Neurology and Cellular & Molecular Physiology, Yale University, New Haven, Connecticut; Veteran's Affairs Medical Center, West Haven, Connecticut; and Departments of Neurology and Molecular Physiology & Biophysics, University of Iowa, Iowa City, Iowa
Michael B Harris - Department of Biology and Wildlife, and Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska
Resource Type: Journal article
Publication Details: Journal of neurophysiology, Vol.114(1), pp.381-389
DOI: 10.1152/jn.00870.2013
PMID: 25878157
PMCID: PMC4507970
NLM abbreviation: J Neurophysiol
ISSN: 0022-3077
eISSN: 1522-1598
Publisher: United States
Grant note: 2U54NS041069 / NINDS NIH HHS R01 HD052772 / NICHD NIH HHS P01 HD036379 / NICHD NIH HHS P01HD36379 / NICHD NIH HHS U01 NS090414 / NINDS NIH HHS R01HD052772 / NICHD NIH HHS
Language: English
Date published: 07/2015
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984020769402771

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