GABAA receptor β1-subunit knock-out mice show increased delta power in NREM sleep and decreased theta power in REM sleep

Abstract

γ-Aminobutyric acid (GABA) acting through heteropentameric GABAA receptors plays a pivotal role in the sleep-promoting circuitry. Whereas the role of the different GABAA receptor α-subunits in sleep regulation and in mediating the effect of benzodiazepines for treatment of insomnia is well-described, the β-subunits are less studied. Here we report the first study characterizing sleep in mice lacking the GABAA receptor β1-subunit (β1−/− mice). We show that β1−/− 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 β1+/+ mice, without any change in the overall sleep-wake architecture. From GABAA receptor-specific autoradiography, it is further demonstrated that functional β1-subunit-containing GABAA receptors display the highest binding levels in the hippocampus and frontal cortex. In conclusion, this study suggests that the GABAA receptor β1-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 GABAA receptor subunits in sleep regulation. In addition, β1−/− mice could provide a useful mouse model for future studies of the physiological role of delta and theta rhythms during sleep.