Genetic Evidence for a Role for Protein Kinase A in the Maintenance of Sleep and Thalamocortical Oscillations

Kevin HELLMAN; Pepe HERNANDEZ; Alice PARK; Ted ABEL

doi:10.1093/sleep/33.1.19

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Genetic Evidence for a Role for Protein Kinase A in the Maintenance of Sleep and Thalamocortical Oscillations

Journal article

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Genetic Evidence for a Role for Protein Kinase A in the Maintenance of Sleep and Thalamocortical Oscillations

Kevin HELLMAN, Pepe HERNANDEZ, Alice PARK and Ted ABEL

Sleep (New York, N.Y.), Vol.33(1), pp.19-28

2010

DOI: 10.1093/sleep/33.1.19

PMCID: PMC2802244

PMID: 20120617

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Abstract

Study objectives: Genetic manipulation of cAMP-dependent protein kinase A (PKA) in Drosophila has implicated an important role for PKA in sleeplwake state regulation. Here, we characterize the role of this signaling pathway in the regulation of sleep using electroencephalographic (EEG) and electromyographic (EMG) recordings in R(AB) transgenic mice that express a dominant negative form of the regulatory subunit of PKA in neurons within cortex and hippocampus. Previous studies have revealed that these mutant mice have reduced PKA activity that results in the impairment of hippocampus-dependent long-term memory and long-lasting forms of hippocampal synaptic plasticity. Design: PKA assays, in situ hybridization, immunoblots, and sleep studies were performed in R(AB) transgenic mice and wild-type control mice. Measurements and results: We have found that R(AB) transgenic mice have reduced PKA activity within cortex and reduced Ser845 phosphorylation of the glutamate receptor subunit GluR1. R(AB) transgenic mice exhibit non-rapid eye movement (NREM) sleep fragmentation and increased amounts of rapid eye movement (REM) sleep relative to wild-type mice. Further, R(AB) transgenic mice have more delta power but less sigma power during NREM sleep relative to wild-type mice. After sleep deprivation, the amounts of NREM and REM sleep were comparable between wild-type and R(AB) transgenic mice. However, the homeostatic rebound of sigma power in R(AB) transgenic mice was reduced. Conclusions: Alterations in cortical synaptic receptors, impairments in sleep continuity, and alterations in sleep oscillations in R(AB) mice imply that PKA is involved not only in synaptic plasticity and memory storage but also in the regulation of sleep/wake states.

Fundamental and applied biological sciences. Psychology

Biological and medical sciences

Behavioral psychophysiology

Psychology. Psychoanalysis. Psychiatry

Psychology. Psychophysiology

Details

Title: Subtitle: Genetic Evidence for a Role for Protein Kinase A in the Maintenance of Sleep and Thalamocortical Oscillations
Creators: Kevin HELLMAN - Department of Neurobiology, University of Chicago, Chicago, IL, United States
Pepe HERNANDEZ - Department of Biology, University of Pennsylvania, Philadelphia, PA, United States
Alice PARK - College of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United States
Ted ABEL - Department of Biology, University of Pennsylvania, Philadelphia, PA, United States
Resource Type: Journal article
Publication Details: Sleep (New York, N.Y.), Vol.33(1), pp.19-28
Publisher: American Academy of Sleep Medicine; Darien, IL
DOI: 10.1093/sleep/33.1.19
PMID: 20120617
PMCID: PMC2802244
ISSN: 0161-8105
eISSN: 1550-9109
Language: English
Date published: 2010
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065838502771

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