Central serotonin neurons are required for arousal to CO2

Gordon F Buchanan; George B Richerson

doi:10.1073/pnas.1004587107

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Central serotonin neurons are required for arousal to CO2

Journal article

Open access

Peer reviewed

Central serotonin neurons are required for arousal to CO2

Gordon F Buchanan and George B Richerson

Proceedings of the National Academy of Sciences - PNAS, Vol.107(37), pp.16354-16359

09/14/2010

DOI: 10.1073/pnas.1004587107

PMCID: PMC2941296

PMID: 20805497

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Abstract

There is a long-standing controversy about the role of serotonin in sleep/wake control, with competing theories that it either promotes sleep or causes arousal. Here, we show that there is a marked increase in wakefulness when all serotonin neurons are genetically deleted in mice hemizygous for ePet1-Cre and homozygous for floxed Lmx1b (Lmx1b(f/f/p)). However, this only occurs at cool ambient temperatures and can be explained by a thermoregulatory defect that leads to an increase in motor activity to generate heat. Because some serotonin neurons are stimulated by CO(2), and serotonin activates thalamocortical networks, we hypothesized that serotonin neurons cause arousal in response to hypercapnia. We found that Lmx1b(f/f/p) mice completely lacked any arousal response to inhalation of 10% CO(2) (with 21% O(2) in balance N(2)) but had normal arousal responses to hypoxia, sound, and air puff. We propose that serotonin neurons mediate the potentially life-saving arousal response to hypercapnia. Impairment of this response may contribute to sudden unexpected death in epilepsy, sudden infant death syndrome, and sleep apnea.

Cold Temperature

Carbon Dioxide - metabolism

Homeodomain Proteins - metabolism

Hypercapnia - genetics

Stress, Physiological

Male

Mice, Transgenic

Transcription Factors - genetics

Homeodomain Proteins - genetics

Transcription Factors - metabolism

Animals

Sleep

Wakefulness

Serotonin - metabolism

Female

LIM-Homeodomain Proteins

Mice

Neurons - metabolism

Hypercapnia - metabolism

Details

Title: Subtitle: Central serotonin neurons are required for arousal to CO2
Creators: Gordon F Buchanan - Departmentsof Neurology, Yale University, New Haven, CT 06520, USA. gordon.buchanan@yale.edu
George B Richerson
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(37), pp.16354-16359
DOI: 10.1073/pnas.1004587107
PMID: 20805497
PMCID: PMC2941296
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Language: English
Date published: 09/14/2010
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984020618502771

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