Preoptic area controls sleep-related seizure onset in a genetic epilepsy mouse model.

In genetic and refractory epileptic patients, seizure activity exhibits sleep-related modulation/regulation and sleep and seizure are intermingled. In this study, by using one het KI mice as a genetic epilepsy model and optogenetic method , we found that subcortical POA neurons were active within epileptic network from the het KI mice and the POA activity preceded epileptic (poly)spike-wave discharges(SWD/PSDs) in the het KI mice. Meanwhile, as expected, the manipulating of the POA activity relatively altered NREM sleep and wake periods in both wt and the het KI mice. Most importantly, the short activation of epileptic cortical neurons alone did not effectively trigger seizure activity in the het KI mice. In contrast, compared to the wt mice, combined the POA nucleus activation and short activation of the epileptic cortical neurons effectively triggered or suppressed epileptic activity in the het KI mice, indicating that the POA activity can control the brain state to trigger seizure incidence in the het KI mice In addition, the suppression of POA nucleus activity decreased myoclonic jerks in the KI mice. Overall, this study discloses an operational mechanism for sleep-dependent seizure incidence in the genetic epilepsy model with the implications for refractory epilepsy. This operational mechanism also underlies myoclonic jerk generation, further with translational implications in seizure treatment for genetic/refractory epileptic patients and with contribution to memory/cognitive deficits in epileptic patients.