Reduced expression of α5GABA_A receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior

A reduction in the activity of GABA_A receptors, particularly α5 subunit-containing GABA_A receptors (α5GABA_ARs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABA_ARs (Gabra5^-/-) exhibit autism-like behaviors and both enhanced and impaired learning and memory, depending on the behavioral task. The aim of this study was to examine the electroencephalogram (EEG) activity and sleep-wake behaviors in Gabra5^-/- mice and wild-type mice. In addition, since some individuals with ASD can exhibit elevated innate immune response, mice were treated with lipopolysaccharide (LPS; 125mg/kg intraperitoneal injection) or vehicle and EEG and sleep-wake patterns were assessed. The results showed that Gabra5^-/- mice (n=3) exhibited elevated 0-2Hz EEG activity during all sleep-wake states (all p<0.04), decreased 8-12Hz EEG activity during REM sleep (p=0.04), and decreased sleep spindles under baseline conditions compared to wild-type controls (n=4) (all p≤0.03). Alterations in EEG activity and sleep-wake behavior were identified in Gabra5^-/- mice following treatment with LPS, however these changes were similar to those in wild-type mice. Our findings support the hypothesis that reduced α5GABA_AR activity contributes to an ASD phenotype. The results also suggest that Gabra5^-/- mice may serve as an animal model for ASD, as assessed through EEG activity and sleep-wake behaviors.