Journal article
Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons
The Journal of neuroscience, Vol.28(10), pp.2495-2505
03/05/2008
DOI: 10.1523/JNEUROSCI.4729-07.2008
PMCID: PMC6671195
PMID: 18322094
Abstract
Serotonergic neurons project widely throughout the CNS and modulate many different brain functions. Particularly important, but controversial, are the contributions of serotonin (5-HT) neurons to respiratory and thermoregulatory control. To better define the roles of 5-HT neurons in breathing and thermoregulation, we took advantage of a unique conditional knock-out mouse in which
Lmx1b
is genetically deleted in
Pet1
-expressing cells (
Lmx1b
f/f/p
), resulting in near-complete absence of central 5-HT neurons. Here, we show that the hypercapnic ventilatory response in adult
Lmx1b
f/f/p
mice was decreased by 50% compared with wild-type mice, whereas baseline ventilation and the hypoxic ventilatory response were normal. In addition,
Lmx1b
f/f/p
mice rapidly became hypothermic when exposed to an ambient temperature of 4°C, decreasing core temperature to 30°C within 120 min. This failure of thermoregulation was caused by impaired shivering and nonshivering thermogenesis, whereas thermosensory perception and heat conservation were normal. Finally, intracerebroventricular infusion of 5-HT stimulated baseline ventilation, and rescued the blunted hypercapnic ventilatory response. These data identify a previously unrecognized role of 5-HT neurons in the CO
2
chemoreflex, whereby they enhance the response of the rest of the respiratory network to CO
2
. We conclude that the proper function of the 5-HT system is particularly important under conditions of environmental stress and contributes significantly to the hypercapnic ventilatory response and thermoregulatory cold defense.
Details
- Title: Subtitle
- Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons
- Creators
- Matthew R Hodges - Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520Glenn J Tattersall - Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada L2S 3A1Michael B Harris - Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska 99775Sean D McEvoy - Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520Diana N Richerson - Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520Evan S Deneris - Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106Randy L Johnson - Department of Biochemistry and Molecular Biology, University of Texas, Houston, Texas 77030Zhou-Feng Chen - Departments of Anesthesiology, Psychiatry, Molecular Biology and Pharmacology, Washington University School of Medicine Pain Center, St. Louis, Missouri 63110, andGeorge B Richerson - Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.28(10), pp.2495-2505
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.4729-07.2008
- PMID
- 18322094
- PMCID
- PMC6671195
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 03/05/2008
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020768002771
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