PT - JOURNAL ARTICLE AU - E Paschen AU - C Elgueta AU - K Heining AU - DM Vieira AU - C Orcinha AU - U Häussler AU - M Bartos AU - U Egert AU - P Janz AU - CA Haas TI - Optogenetic low-frequency stimulation of dentate granule cells prevents seizure generation in experimental epilepsy AID - 10.1101/2020.01.09.900084 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.01.09.900084 4099 - http://biorxiv.org/content/early/2020/01/10/2020.01.09.900084.short 4100 - http://biorxiv.org/content/early/2020/01/10/2020.01.09.900084.full AB - Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults and is typically associated with hippocampal sclerosis and drug-resistant seizures. As an alternative to curative epilepsy surgery, brain stimulation evolves as a promising approach for seizure-interference. However, particularly in MTLE with severe hippocampal sclerosis, current stimulation protocols are often not effective. Here, we show that optogenetic low-frequency stimulation (oLFS) of entorhinal afferents exhibits unprecedented anti-ictogenic effects in chronically epileptic mice. Photostimulation at 1 Hz resulted in an almost complete suppression of focal seizures, independent of the degree of hippocampal sclerosis. Furthermore, by performing oLFS for 30 min before a pro-convulsive stimulus, seizure generalization was successfully prevented. Finally, acute slice experiments revealed a decreased excitability upon oLFS, which may partially explain the observed anti-epileptic effects. Taken together, our results suggest that oLFS of entorhinal afferents constitutes a promising approach for seizure control in MTLE.