Spontaneous spike-and-wave discharges during sleep in mice: circadian distribution and impact on sleep quality

TL;DR

This study characterizes spontaneous spike-and-wave discharges in JAX mice during sleep, revealing their circadian pattern and impact on sleep quality.

Contribution

The study introduces JAX mice as a novel model for sleep-related spike-and-wave discharges with a distinct circadian distribution.

Findings

JAX mice show numerous SWDs during slow-wave sleep without convulsions.

SWDs in JAX mice follow a circadian pattern, peaking at the end of the rest period.

JAX mice have altered sleep architecture with reduced slow-wave sleep and more sleep state transitions.

Abstract

Spike-wave discharges (SWDs) are pathological brain oscillations caused by abnormal thalamocortical synchronization and are a hallmark of several epileptic syndromes. While several experimental models are characterized by SWDs during wakefulness and mimic several key features of absence epilepsy, the spontaneous occurrence of SWDs during sleep has been reported in a limited number of studies. Here, we report a comprehensive characterization of the electrophysiological profile and sleep-wake cycle of a mouse strain previously shown to present sleep-associated SWDs.

Inbred AJ mice from Jackson Laboratory (JAX) and matched control mice were instrumented for chronic video-EEG/EMG recordings. Data obtained during two 24-hour recording sessions were analyzed to characterize both the sleep-wake cycle and abnormal electrical activity.

Unlike control animals, JAX mice consistently displayed numerous SWDs. The vast majority of episodes occurred during slow-wave sleep (SWS) without overt convulsive manifestations. JAX mice exhibited a reduction in SWS, spent more time in paradoxical sleep, and showed more transitions between vigilance states than controls. Interestingly, SWD events were distributed in a circadian fashion, peaking around the end of the rest period.

Alongside previously characterized models, the consistent and spontaneous occurrence of SWDs during SWS makes the JAX mouse a viable experimental model to understand the mechanisms behind sleep-related SWDs. The results, including the peculiar circadian distribution of SWDs, pave the way for further studies addressing a fundamental pathogenetic conundrum, i.e., why is epileptiform activity specifically concentrated in SWS.

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