期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 54, 期 2, 页码 4445-4455出版社
WILEY
DOI: 10.1111/ejn.15267
关键词
addiction; GABAergic circuits; knock‐ out mice; sleep‐ wake cycle
资金
- Horslev--Fonden
- Drug Research Academy, Kobenhavns Universitet
- Lundbeckfonden [R133--A12270, R230--2016--2562, R277--2018--260]
This study reveals that the GABA(A) receptor beta(1)-subunit does not play a crucial role in sleep initiation or maintenance, but instead regulates the power spectrum and expression of theta rhythm. Functional beta(1)-subunit-containing GABA(A) receptors exhibit highest binding levels in the hippocampus and frontal cortex, indicating their significance in modulating sleep patterns.
gamma-Aminobutyric acid (GABA) acting through heteropentameric GABA(A) receptors plays a pivotal role in the sleep-promoting circuitry. Whereas the role of the different GABA(A) receptor alpha-subunits in sleep regulation and in mediating the effect of benzodiazepines for treatment of insomnia is well-described, the beta-subunits are less studied. Here we report the first study characterizing sleep in mice lacking the GABA(A) receptor beta(1)-subunit (beta(-/-)(1) mice). We show that beta(-/-)(1) mice have a distinct and abnormal sleep phenotype characterized by increased delta power in non-rapid eye movement (NREM) sleep and decreased theta activity in rapid eye movement (REM) sleep compared to beta(+/+)(1) mice, without any change in the overall sleep-wake architecture. From GABA(A) receptor-specific autoradiography, it is further demonstrated that functional beta(1)-subunit-containing GABA(A) receptors display the highest binding levels in the hippocampus and frontal cortex. In conclusion, this study suggests that the GABA(A) receptor beta(1)-subunit does not play an important role in sleep initiation or maintenance but instead regulates the power spectrum and especially the expression of theta rhythm. This provides new knowledge on the complex role of GABA(A) receptor subunits in sleep regulation. In addition, beta(-/-)(1) mice could provide a useful mouse model for future studies of the physiological role of delta and theta rhythms during sleep.
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