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

Federico Del Gallo¹Valentina Salari²Marika Maggia¹Manal Salmi^3,4Marina Bentivoglio¹Paolo Francesco Fabene²Pierre Szepetowski^3*Giuseppe Bertini^1*

• ¹Universita degli Studi di Verona Dipartimento di Neuroscienze Biomedicina e Movimento, Verona, Italy
• ²Universita degli Studi di Verona Dipartimento di Ingegneria per la Medicina di Innovazione, Verona, Italy
• ³National Institute of Health and Medical Research INSERM, Joint Research Unit UMR 1249, Mediterranean Institute of Neurobiology INMED, Aix‐Marseille University, Marseille, France
• ⁴Albert Einstein College of Medicine Dominick P Purpura Department of Neuroscience, New York, United States

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.