The absence of Neuroligin-1 shapes wake/sleep architecture, rhythmic and arrhythmic activities of the electrocorticogram in female mice

Associated to glutamatergic neurotransmission, Neuroligin-1 (NLGN1) is a synaptic adhesion molecule with roles in the regulation of behavioral states and cognitive function. It was shown to shape electrocorticographic (ECoG) activity during wakefulness and sleep in male mice, including aperiodic activity under baseline conditions. Given that the expression of Neuroligins (Nlgn) differs between sexes, we here aim to characterize the impact of the absence of NLGN1 on the wakefulness and sleep architecture, rhythmic and arrhythmic activity dynamics, and responses to sleep deprivation in female animals. Nlgn1 knockout (KO) female mice and wild-type (WT) female littermates were implanted with ECoG electrodes, and ECoG signals were recorded for 48 hours comprising a 24-hour baseline, followed by a 6-hour sleep deprivation and 18 hours of undisturbed recovery (REC). Time spent in wakefulness, slow wave sleep (SWS) and paradoxical sleep (PS), and their alternation were interrogated, and ECoG activities were quantified using a standard spectral analysis and a multifractal analysis. Nlgn1 KO females spent more time in PS during the light period under baseline in comparison to WT females. This difference was observed along with more PS bouts and a shorter overall PS bout duration, indicative of a fragmented PS. Additionally, Nlgn1 KO females displayed less ECoG power between 8 and 13 Hz during wake, less power between 1.25 and 3.5 Hz during PS, and more between 2.5 and 3.75 Hz during SWS in comparison to WT. Under both baseline and REC, NLGN1 absence in females was significantly associated with a higher value of the most prevalent Hurst exponent (Hm) during SWS, which points to a higher persistence across scales of ECoG aperiodic activity. Indications for alterations in the daily dynamics of the Dispersion of Hurst exponents around Hm were also found during SWS in KO females. The present study highlights differences in wake/sleep architecture, and in periodic (rhythmic) and aperiodic (arrhythmic/multifractal) activities in female mice lacking NLGN1. These findings provide additional support to a role for NLGN1 in shaping the ECoG organization, in particular during sleep, and will help understanding the origin of sleep disturbances in neuropsychiatric diseases.