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Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1 2
Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293636/ https://www.ncbi.nlm.nih.gov/pubmed/25599088 http://dx.doi.org/10.1523/ENEURO.0005-14.2014 |
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author | Krook-Magnuson, Esther Szabo, Gergely G. Armstrong, Caren Oijala, Mikko Soltesz, Ivan |
author_facet | Krook-Magnuson, Esther Szabo, Gergely G. Armstrong, Caren Oijala, Mikko Soltesz, Ivan |
author_sort | Krook-Magnuson, Esther |
collection | PubMed |
description | Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizures. Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures during the chronic phase of the disorder. We further report that the direction of modulation as well as the location of intervention within the cerebellum can affect the outcome of intervention. Specifically, on-demand optogenetic excitation or inhibition of parvalbumin-expressing neurons, including Purkinje cells, in the lateral or midline cerebellum results in a decrease in seizure duration. In contrast, a consistent reduction in spontaneous seizure frequency occurs uniquely with on-demand optogenetic excitation of the midline cerebellum, and was not seen with intervention directly targeting the hippocampal formation. These findings demonstrate that the cerebellum is a powerful modulator of temporal lobe epilepsy, and that intervention targeting the cerebellum as a potential therapy for epilepsy should be revisited. |
format | Online Article Text |
id | pubmed-4293636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-42936362015-01-14 Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1 2 Krook-Magnuson, Esther Szabo, Gergely G. Armstrong, Caren Oijala, Mikko Soltesz, Ivan eNeuro New Research Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizures. Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures during the chronic phase of the disorder. We further report that the direction of modulation as well as the location of intervention within the cerebellum can affect the outcome of intervention. Specifically, on-demand optogenetic excitation or inhibition of parvalbumin-expressing neurons, including Purkinje cells, in the lateral or midline cerebellum results in a decrease in seizure duration. In contrast, a consistent reduction in spontaneous seizure frequency occurs uniquely with on-demand optogenetic excitation of the midline cerebellum, and was not seen with intervention directly targeting the hippocampal formation. These findings demonstrate that the cerebellum is a powerful modulator of temporal lobe epilepsy, and that intervention targeting the cerebellum as a potential therapy for epilepsy should be revisited. Society for Neuroscience 2014-11-12 /pmc/articles/PMC4293636/ /pubmed/25599088 http://dx.doi.org/10.1523/ENEURO.0005-14.2014 Text en Copyright © 2014 Krook-Magnuson et al. http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License Attribution-Noncommercial 4.0 International (http://creativecommons.org/licenses/by-nc/4.0/) which permits noncommercial reuse provided that the original work is properly attributed. |
spellingShingle | New Research Krook-Magnuson, Esther Szabo, Gergely G. Armstrong, Caren Oijala, Mikko Soltesz, Ivan Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1 2 |
title | Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1
2
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title_full | Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1
2
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title_fullStr | Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1
2
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title_full_unstemmed | Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1
2
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title_short | Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1
2
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title_sort | cerebellar directed optogenetic intervention inhibits spontaneous hippocampal seizures in a mouse model of temporal lobe epilepsy1
2 |
topic | New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293636/ https://www.ncbi.nlm.nih.gov/pubmed/25599088 http://dx.doi.org/10.1523/ENEURO.0005-14.2014 |
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