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

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.

Fxr1 regulates sleep and synaptic homeostasis

“…The surgery combined viral delivery to the frontal cortex with electrode implantation for EEG/EMG recording that has been performed as described previously (El Helou et al , 2013; Freyburger et al , 2016; Seok et al , 2018). Mice were anesthetized (ketamine/xylazine 120/10 mg/kg, intraperitoneal injection) and placed in a stereotaxic frame.…”

Shank3 modulates sleep and expression of circadian transcription factors

“…The opposite phenotype was reported in a Fragile X mouse model, displaying instead an age-dependent reduction in activity during the light phase (i.e the mouse subjective night) (Boone et al, 2018). Neuroligin 1 knockout mice spend more time asleep (El Helou et al, 2013), but mice with mutations in Neuroligin 2 spend less time asleep and more time awake (Seok et al, 2018). Mice with a missense mutation in Neuroligin 3 show normal sleep behavior (Liu et al, 2017), but rats with a deletion mutation in Neuroligin 3 spend less time in non-rapid eye movement (NREM) sleep than wild type rats (Thomas et al, 2017).…”

Sleep, brain development, and autism spectrum disorders: Insights from animal models

“…For example, the mutant rat models of CDFE (Cntnap2) show longer waking periods whereas the mutant mice show fragmented wakefulness (Thomas, Schwartz, Saxe, & Kilduff, 2017). The Neuroligin-1 knockout mice report decreased wakefulness, whereas the Neuroligin-2 knockout mice have increased wakefulness and the Neuroligin-3 mutant mice have no changes in sleep state (El Helou et al, 2013;Liu et al, 2017;Seok et al, 2018;Thomas et al, 2017). It is also important to note that based on the SFARI gene evidence scores, not all genes have the same strength of evidence linking them to ASD which could be a factor affecting the variability in data.…”