Central serotonin neurons are required for arousal to CO2

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 ePet...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-09, Vol.107 (37), p.16354-16359
Main Authors: Buchanan, Gordon F, Richerson, George B
Format: Article
Language:English
Subjects:
Animals
Apnea
Arousal
Biological Sciences
Carbon dioxide
Carbon Dioxide - metabolism
Cold Temperature
Cortex
Epilepsy
Female
Heat
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Hypercapnia
Hypercapnia - genetics
Hypercapnia - metabolism
Hypoxia
Inhalation
LIM-Homeodomain Proteins
Male
Mice
Mice, Transgenic
Motor activity
Neurons
Neurons - metabolism
Serotonin
Serotonin - metabolism
Sleep
Sleep and wakefulness
Sleep disorders
Sound
Stress, Physiological
Sudden-infant-death syndrome
Temperature effects
Thalamus
Transcription Factors - genetics
Transcription Factors - metabolism
Wakefulness
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1004587107