Reduced expression of α5GABA receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior.

A reduction in the activity of GABA receptors, particularly α5 subunit-containing GABA receptors (α5GABARs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABARs (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 α5GABAR 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.