Sex-dependent effects of Neuroligin-2 absence on wake/sleep architecture and electrocorticographic spectral and multifractal activities

Neuroligin-2 (NLGN2) is a synaptic adhesion protein shaping GABAergic neurotransmission that has been linked to neurodevelopmental disorders. The absence of NLGN2 in male mice increases time spent awake, decreases time spent in slow wave sleep, and alters electrocorticographic (ECoG) activity. Whether the lack of NLGN2 also impacts wake/sleep states in females remains to be established. We aimed to compare sexes for the effects of NLGN2 absence on the wake/sleep architecture, spectral and multifractal ECoG activities. Nlgn2 knockout (KO) mice and wild-type littermates were implanted with ECoG electrodes, and ECoG signals were recorded for 48 hours. Nlgn2 KO mice of both sexes spent more time awake and less time in slow wave and paradoxical sleep, with KO males spending less time in paradoxical sleep during both the light and dark periods compared to wild-type males (difference only during the dark in females). Nlgn2 KO animals displayed longer wakefulness and shorter slow wave and paradoxical sleep episodes, and KO males (but not females) showed more wake and slow wave sleep episodes during the light period. Also, mutant animals (both sexes) showed widespread differences in wake/sleep spectral activity when compared to wild-type mice, notably a slower theta peak frequency during paradoxical sleep. The most prominent Hurst exponent was significantly increased in Nlgn2 KO animals during all states, and Hurst exponents were less dispersed during paradoxical sleep only in KO females. The findings indicate that effects of NLGN2 absence on wake/sleep phenotypes differ between sexes, and could help understanding sleep disturbances in neurodevelopmental disorders.