Hippocampal Area CA2 Controls Seizure Dynamics, Interictal EEG Abnormalities and Social Comorbidity in Mouse Models of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, abnormal activity between seizures, and impaired behavior. CA2 pyramidal neurons (PNs) are potentially important because inhibiting them with a chemogenetic approach reduces seizure frequency in a mouse model of TLE. However, whether seizures could be stopped by timing inhibition just as a seizure begins is unclear. Furthermore, whether inhibition would reduce the cortical and motor manifestations of seizures are not clear. Finally, whether interictal EEG abnormalities and TLE comorbidities would be improved are unknown. Therefore, real-time optogenetic silencing of CA2 PNs during seizures, interictal activity and behavior were studied in 2 mouse models of TLE. CA2 silencing significantly reduced seizure duration and time spent in convulsive behavior. Interictal spikes and high frequency oscillations were significantly reduced, and social behavior was improved. Therefore, brief focal silencing of CA2 PNs reduces seizures, their propagation, and convulsive manifestations, improves interictal EEG, and ameliorates social comorbidities.HIGHLIGHTS ### Competing Interest StatementThe authors have declared no competing interest.* DG : Dentate gyrus EEG : Electroencephalography HFOs : High frequency oscillations IIS : Interictal spikes PNs : Pyramidal neurons TLE : Temporal lobe epilepsy