Optogenetic activation of septal inhibitory cells abates focal seizures.

Emerging evidence suggest that the medial septum can control seizures occurring in focal epileptic disorders, thus representing a therapeutic target. Therefore, we investigated whether continuous optogenetic activation of inhibitory parvalbumin-positive (PV) interneurons in the medial septum can reduce the occurrence of spontaneous seizures in the pilocarpine model of mesial temporal lobe epilepsy (MTLE). Light pulses (450 nm, 25 mW, 20 ms pulse duration) were delivered at 0.5 Hz (5 min ON, 10 min OFF), with a laser diode fiber light source between day 8 and 12 after status epilepticus (SE) in PV-ChR2 mice (n = 8). Seizure rates were significantly lower during time-periods of optogenetic stimulation (day 8-12) compared to before implementa-tion of optogenetics (day 4-7) (p < 0.05). Moreover, between day 13 and 21 after SE, seizure rates were still significantly lower compared to before optogenetic stimulation (i.e., between day 4 and 7) (p < 0.05). No seizures were recorded between day 10 and 12 in all animals, and no seizures occurred up to three days after the end of optogenetic stimulation (day 13-15). Our findings indicate that activation of PV-positive interneurons in the medial septum abates seizures in the pilocarpine model of MTLE. Moreover, the persisting anti-ictogenic effects suggests that stimulation of the medial septum could alter the progression of MTLE.