The effect of Neuroligin-2 absence on sleep architecture and electroencephalographic activity in mice

Bong Soo Seok,Valérie Mongrain,Erika Bélanger-Nelson,Steve Gibbs,Chloé Provost

doi:10.1186/s13041-018-0394-3

Abstract

Sleep disorders are comorbid with most psychiatric disorders, but the link between these is not well understood. Neuroligin-2 (NLGN2) is a cell adhesion molecule that plays roles in synapse formation and neurotransmission. Moreover, NLGN2 has been associated with psychiatric disorders, but its implication in sleep remains underexplored. In the present study, the effect of Nlgn2 knockout (Nlgn2−/−) on sleep architecture and electroencephalographic (EEG) activity in mice has been investigated. The EEG and electromyogram (EMG) were recorded in Nlgn2−/− mice and littermates for 24 h from which three vigilance states (i.e., wakefulness, rapid eye movement [REM] sleep, non-REM [NREM] sleep) were visually identified. Spectral analysis of the EEG was performed for the three states. Nlgn2−/− mice showed more wakefulness and less NREM and REM sleep compared to wild-type (Nlgn2+/+) mice, especially during the dark period. This was accompanied by changes in the number and duration of individual episodes of wakefulness and sleep, indexing changes in state consolidation, as well as widespread changes in EEG spectral activity in all states. Abnormal ‘hypersynchronized’ EEG events have also been observed predominantly in Nlgn2−/− mice. These events were mainly observed during wakefulness and REM sleep. In addition, Nlgn2−/− mice showed alterations in the daily time course of NREM sleep delta (1–4 Hz) activity, pointing to modifications in the dynamics of sleep homeostasis. These data suggest that NLGN2 participates in the regulation of sleep duration as well as EEG activity during wakefulness and sleep.

Highlights

Research from the last decades suggests that people suffering from a sleep disorder such as insomnia show higher risk of developing medical and/or psychiatric disorders [1, 2]
More time spent awake in Nlgn2−/− mice During the full 24-h recording, Nlgn2−/− mice spent more time in wakefulness and less time in Rapid eye movement (REM) sleep compared to Nlgn2+/+ littermates (Fig. 1a)
Less REM sleep in both Nlgn2−/ − and Nlgn2+/− mice compared to Nlgn2+/+ mice was observed for the 12-h Light period, while less REM sleep in Nlgn2−/− mice compared to Nlgn2+/− and Nlgn2+/+

Summary

Introduction

Research from the last decades suggests that people suffering from a sleep disorder such as insomnia show higher risk of developing medical and/or psychiatric disorders [1, 2]. Neurodevelopmental psychiatric disorders in particular, such as ASDs and schizophrenia, have been proposed to originate from changes in the relative. Research in both rodents and flies has provided support for an implication of specific NLGNs in sleep. The absence of NLGN1 (knockout, KO) results in a decreased duration of wakefulness and increased duration of NREM sleep accompanied by changes in wakefulness and NREM sleep quality as quantified using EEG spectral analysis and slow wave detection [10, 11]. Nlgn3R451C knock-in mice, carrying an ASD-associated missence mutation, have been shown to exhibit normal sleep architecture but a decrease in low frequency (< 10 Hertz [Hz]) activity during NREM sleep [13].

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