Tonic-clonic seizures induce hypersomnia and suppress rapid eye movement sleep in mouse models of epilepsy.

The reciprocal relationship between sleep and epilepsy has been reported by numerous clinical studies. However, the underlying neural mechanisms are poorly understood. Animal models of epilepsy are powerful tools to tackle this question. A lagging research area is the understudied sleep in epilepsy models. Here, we characterize sleep architecture and its relationship with seizures in a mouse model of sleep-related hypermotor epilepsy, caused by mutation of KCNT1. We demonstrated that nocturnal tonic-clonic seizures induce more non-rapid eye movement (NREM) sleep but suppress rapid eye movement (REM) sleep, resulting in altered sleep architecture in this mouse model. Importantly, the seizure number is quantitatively anticorrelated with the amount of REM sleep. Strikingly, this modulation of NREM and REM sleep states can be repeated in another mouse model of epilepsy with diurnal tonic-clonic seizures. Together, our findings provide evidence from rodent models to substantiate the close interplay between sleep and epilepsy, which lays the ground for mechanistic studies.