TY - JOUR TI - Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy AU - Paschen, Enya AU - Elgueta, Claudio AU - Heining, Katharina AU - Vieira, Diego M AU - Kleis, Piret AU - Orcinha, Catarina AU - Häussler, Ute AU - Bartos, Marlene AU - Egert, Ulrich AU - Janz, Philipp AU - Haas, Carola A A2 - Huguenard, John R A2 - Kadam, Shilpa D VL - 9 PY - 2020 DA - 2020/12/22 SP - e54518 C1 - eLife 2020;9:e54518 DO - 10.7554/eLife.54518 UR - https://doi.org/10.7554/eLife.54518 AB - Mesial temporal lobe epilepsy (MTLE) is the most common form of focal, pharmacoresistant epilepsy in adults and is often associated with hippocampal sclerosis. Here, we established the efficacy of optogenetic and electrical low-frequency stimulation (LFS) in interfering with seizure generation in a mouse model of MTLE. Specifically, we applied LFS in the sclerotic hippocampus to study the effects on spontaneous subclinical and evoked generalized seizures. We found that stimulation at 1 Hz for 1 hr resulted in an almost complete suppression of spontaneous seizures in both hippocampi. This seizure-suppressive action during daily stimulation remained stable over several weeks. Furthermore, LFS for 30 min before a pro-convulsive stimulus successfully prevented seizure generalization. Finally, acute slice experiments revealed a reduced efficacy of perforant path transmission onto granule cells upon LFS. Taken together, our results suggest that hippocampal LFS constitutes a promising approach for seizure control in MTLE. KW - dentate gyrus KW - kainate KW - optogenetics KW - deep brain stimulation KW - channelrhodopsin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -