Journal article
Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition
Science (American Association for the Advancement of Science), Vol.333(6042), pp.637-642
07/29/2011
DOI: 10.1126/science.1205295
PMCID: PMC3729433
PMID: 21798952
Abstract
Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved but constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a synthetic GPCR (Di)-based neuronal silencing tool, mouse
RC∷FPDi
, designed for cell type-specific, ligand (clozapine-N-oxide, CNO)-inducible and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, CNO administration by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue CO
2
elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO
2
/acidosis. Body thermoregulation at room temperature was also disrupted following CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.
Details
- Title: Subtitle
- Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition
- Creators
- Russell Ray - Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, U.S.AAndrea Corcoran - Department of Physiology, Dartmouth Medical School, One Medical Center Road, Lebanon, NH 03756-0001, U.S.ARachael Brust - Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, U.S.AJun Chul Kim - Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ontario M5S 3G3, CanadaGeorge B Richerson - Department of Neurology, UI Hospitals and Clinics, 200 Hawkins Drive, 2007 RCP, Iowa City, Iowa 52242, U.S.AEugene Nattie - Department of Physiology, Dartmouth Medical School, One Medical Center Road, Lebanon, NH 03756-0001, U.S.ASusan M Dymecki - Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, U.S.A
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.333(6042), pp.637-642
- DOI
- 10.1126/science.1205295
- PMID
- 21798952
- PMCID
- PMC3729433
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Grant note
- P01 HD036379 || HD / National Institute of Child Health & Human Development : NICHD R01 HD052772 || HD / National Institute of Child Health & Human Development : NICHD R21 DA023643 || DA / National Institute on Drug Abuse : NIDA R21 MH083613 || MH / National Institute of Mental Health : NIMH R01 HL028066 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 07/29/2011
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020503602771
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