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Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling

BACKGROUND: Epilepsy, a prevalent neurological disorder, appears self-termination. The endogenous mechanism for seizure self-termination remains to be addressed in order to develop new strategies for epilepsy treatment. We aim to examine the role of activity-induced spontaneous spikes at GABAergic n...

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Detalles Bibliográficos
Autores principales: Lu, Wei, Feng, Jing, Wen, Bo, Wang, Kewei, Wang, Jin-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464796/
https://www.ncbi.nlm.nih.gov/pubmed/28427143
http://dx.doi.org/10.18632/oncotarget.15660
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author Lu, Wei
Feng, Jing
Wen, Bo
Wang, Kewei
Wang, Jin-Hui
author_facet Lu, Wei
Feng, Jing
Wen, Bo
Wang, Kewei
Wang, Jin-Hui
author_sort Lu, Wei
collection PubMed
description BACKGROUND: Epilepsy, a prevalent neurological disorder, appears self-termination. The endogenous mechanism for seizure self-termination remains to be addressed in order to develop new strategies for epilepsy treatment. We aim to examine the role of activity-induced spontaneous spikes at GABAergic neurons as an endogenous mechanism in the seizure self-termination. METHODS AND RESULTS: Neuronal spikes were induced by depolarization pulses at cortical GABAergic neurons from temporal lobe epilepsy patients and mice, in which some of these neurons fired activity-induced spontaneous spikes. Neural networks including excitatory and inhibitory neurons were computationally constructed, and their functional properties were based on our studies from whole-cell recordings. With the changes in the portion and excitability of inhibitory neurons that generated activity-induced spontaneous spike, the efficacies to suppress synchronous seizure activity were analyzed, such as its onset time, decay slope and spike frequency. The increases in the proportion and excitability of inhibitory neurons that generated activity-induced spontaneous spikes effectively suppressed seizure activity in neural networks. These factors synergistically strengthened the efficacy of seizure activity suppression. CONCLUSION: Our study supports a notion that activity-induced spontaneous spikes in GABAergic neurons may be an endogenous mechanism for seizure self-termination. A potential therapeutic strategy for epilepsy is to upregulate the cortical inhibitory neurons that generate activity-induced spontaneous spikes.
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spelling pubmed-54647962017-06-21 Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling Lu, Wei Feng, Jing Wen, Bo Wang, Kewei Wang, Jin-Hui Oncotarget Research Paper: Pathology BACKGROUND: Epilepsy, a prevalent neurological disorder, appears self-termination. The endogenous mechanism for seizure self-termination remains to be addressed in order to develop new strategies for epilepsy treatment. We aim to examine the role of activity-induced spontaneous spikes at GABAergic neurons as an endogenous mechanism in the seizure self-termination. METHODS AND RESULTS: Neuronal spikes were induced by depolarization pulses at cortical GABAergic neurons from temporal lobe epilepsy patients and mice, in which some of these neurons fired activity-induced spontaneous spikes. Neural networks including excitatory and inhibitory neurons were computationally constructed, and their functional properties were based on our studies from whole-cell recordings. With the changes in the portion and excitability of inhibitory neurons that generated activity-induced spontaneous spike, the efficacies to suppress synchronous seizure activity were analyzed, such as its onset time, decay slope and spike frequency. The increases in the proportion and excitability of inhibitory neurons that generated activity-induced spontaneous spikes effectively suppressed seizure activity in neural networks. These factors synergistically strengthened the efficacy of seizure activity suppression. CONCLUSION: Our study supports a notion that activity-induced spontaneous spikes in GABAergic neurons may be an endogenous mechanism for seizure self-termination. A potential therapeutic strategy for epilepsy is to upregulate the cortical inhibitory neurons that generate activity-induced spontaneous spikes. Impact Journals LLC 2017-02-23 /pmc/articles/PMC5464796/ /pubmed/28427143 http://dx.doi.org/10.18632/oncotarget.15660 Text en Copyright: © 2017 Lu et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper: Pathology
Lu, Wei
Feng, Jing
Wen, Bo
Wang, Kewei
Wang, Jin-Hui
Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling
title Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling
title_full Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling
title_fullStr Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling
title_full_unstemmed Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling
title_short Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling
title_sort activity-induced spontaneous spikes in gabaergic neurons suppress seizure discharges: an implication of computational modeling
topic Research Paper: Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464796/
https://www.ncbi.nlm.nih.gov/pubmed/28427143
http://dx.doi.org/10.18632/oncotarget.15660
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