RT Journal Article
SR Electronic
T1 Optogenetic low-frequency stimulation of dentate granule cells prevents seizure generation in experimental epilepsy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.09.900084
DO 10.1101/2020.01.09.900084
A1 E Paschen
A1 C Elgueta
A1 K Heining
A1 DM Vieira
A1 C Orcinha
A1 U Häussler
A1 M Bartos
A1 U Egert
A1 P Janz
A1 CA Haas
YR 2020
UL http://biorxiv.org/content/early/2020/01/10/2020.01.09.900084.abstract
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.