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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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Autores principales: Paschen, Enya, Elgueta, Claudio, Heining, Katharina, Vieira, Diego M, Kleis, Piret, Orcinha, Catarina, Häussler, Ute, Bartos, Marlene, Egert, Ulrich, Janz, Philipp, Haas, Carola A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800381/
https://www.ncbi.nlm.nih.gov/pubmed/33349333
http://dx.doi.org/10.7554/eLife.54518
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author Paschen, Enya
Elgueta, Claudio
Heining, Katharina
Vieira, Diego M
Kleis, Piret
Orcinha, Catarina
Häussler, Ute
Bartos, Marlene
Egert, Ulrich
Janz, Philipp
Haas, Carola A
author_facet Paschen, Enya
Elgueta, Claudio
Heining, Katharina
Vieira, Diego M
Kleis, Piret
Orcinha, Catarina
Häussler, Ute
Bartos, Marlene
Egert, Ulrich
Janz, Philipp
Haas, Carola A
author_sort Paschen, Enya
collection PubMed
description 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.
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spelling pubmed-78003812021-01-13 Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy Paschen, Enya Elgueta, Claudio Heining, Katharina Vieira, Diego M Kleis, Piret Orcinha, Catarina Häussler, Ute Bartos, Marlene Egert, Ulrich Janz, Philipp Haas, Carola A eLife Neuroscience 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. eLife Sciences Publications, Ltd 2020-12-22 /pmc/articles/PMC7800381/ /pubmed/33349333 http://dx.doi.org/10.7554/eLife.54518 Text en © 2020, Paschen et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Paschen, Enya
Elgueta, Claudio
Heining, Katharina
Vieira, Diego M
Kleis, Piret
Orcinha, Catarina
Häussler, Ute
Bartos, Marlene
Egert, Ulrich
Janz, Philipp
Haas, Carola A
Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
title Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
title_full Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
title_fullStr Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
title_full_unstemmed Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
title_short Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
title_sort hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800381/
https://www.ncbi.nlm.nih.gov/pubmed/33349333
http://dx.doi.org/10.7554/eLife.54518
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