Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy

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...

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Bibliographic Details
Published in:eLife 2020-12, Vol.9
Main Authors: Paschen, Enya, Elgueta, Claudio, Heining, Katharina, Vieira, Diego M, Kleis, Piret, Orcinha, Catarina, Häussler, Ute, Bartos, Marlene, Egert, Ulrich, Janz, Philipp, Haas, Carola A
Format: Article
Language:English
Subjects:
Animals
channelrhodopsin
deep brain stimulation
dentate gyrus
Disease Models, Animal
Electric Stimulation - methods
Epilepsy, Temporal Lobe - complications
Epilepsy, Temporal Lobe - physiopathology
Hippocampus - physiopathology
kainate
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuroscience
optogenetics
Seizures - etiology
Seizures - physiopathology
Seizures - prevention & control
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.54518