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GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study

The role of GABAergic neurotransmission on epileptogenesis has been the subject of speculation according to different approaches. However, it is a very complex task to specifically consider the action of the GABAa neurotransmitter, which, in its dependence on the intracellular level of Cl(−), can ch...

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Autores principales: França, Keite Lira de Almeida, de Almeida, Antônio-Carlos Guimarães, Saddow, Stephen E., Santos, Luiz Eduardo Canton, Scorza, Carla Alessandra, Scorza, Fulvio Alexandre, Rodrigues, Antônio Márcio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843660/
https://www.ncbi.nlm.nih.gov/pubmed/29520076
http://dx.doi.org/10.1038/s41598-018-22581-6
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author França, Keite Lira de Almeida
de Almeida, Antônio-Carlos Guimarães
Saddow, Stephen E.
Santos, Luiz Eduardo Canton
Scorza, Carla Alessandra
Scorza, Fulvio Alexandre
Rodrigues, Antônio Márcio
author_facet França, Keite Lira de Almeida
de Almeida, Antônio-Carlos Guimarães
Saddow, Stephen E.
Santos, Luiz Eduardo Canton
Scorza, Carla Alessandra
Scorza, Fulvio Alexandre
Rodrigues, Antônio Márcio
author_sort França, Keite Lira de Almeida
collection PubMed
description The role of GABAergic neurotransmission on epileptogenesis has been the subject of speculation according to different approaches. However, it is a very complex task to specifically consider the action of the GABAa neurotransmitter, which, in its dependence on the intracellular level of Cl(−), can change its effect from inhibitory to excitatory. We have developed a computational model that represents the dentate gyrus and is composed of three different populations of neurons (granule cells, interneurons and mossy cells) that are mutually interconnected. The interconnections of the neurons were based on compensation theory with Hebbian and anti-Hebbian rules. The model also incorporates non-synaptic mechanisms to control the ionic homeostasis and was able to reproduce ictal discharges. The goal of the work was to investigate the hypothesis that the observed aberrant sprouting is promoted by GABAa excitatory action. Conjointly with the abnormal sprouting of the mossy fibres, the simulations show a reduction of the mossy cells connections in the network and an increased inhibition of the interneurons as a response of the neuronal network to control the activity. This finding contributes to increasing the changes in the connectivity of the neuronal circuitry and to increasing the epileptiform activity occurrences.
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spelling pubmed-58436602018-03-14 GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study França, Keite Lira de Almeida de Almeida, Antônio-Carlos Guimarães Saddow, Stephen E. Santos, Luiz Eduardo Canton Scorza, Carla Alessandra Scorza, Fulvio Alexandre Rodrigues, Antônio Márcio Sci Rep Article The role of GABAergic neurotransmission on epileptogenesis has been the subject of speculation according to different approaches. However, it is a very complex task to specifically consider the action of the GABAa neurotransmitter, which, in its dependence on the intracellular level of Cl(−), can change its effect from inhibitory to excitatory. We have developed a computational model that represents the dentate gyrus and is composed of three different populations of neurons (granule cells, interneurons and mossy cells) that are mutually interconnected. The interconnections of the neurons were based on compensation theory with Hebbian and anti-Hebbian rules. The model also incorporates non-synaptic mechanisms to control the ionic homeostasis and was able to reproduce ictal discharges. The goal of the work was to investigate the hypothesis that the observed aberrant sprouting is promoted by GABAa excitatory action. Conjointly with the abnormal sprouting of the mossy fibres, the simulations show a reduction of the mossy cells connections in the network and an increased inhibition of the interneurons as a response of the neuronal network to control the activity. This finding contributes to increasing the changes in the connectivity of the neuronal circuitry and to increasing the epileptiform activity occurrences. Nature Publishing Group UK 2018-03-08 /pmc/articles/PMC5843660/ /pubmed/29520076 http://dx.doi.org/10.1038/s41598-018-22581-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
França, Keite Lira de Almeida
de Almeida, Antônio-Carlos Guimarães
Saddow, Stephen E.
Santos, Luiz Eduardo Canton
Scorza, Carla Alessandra
Scorza, Fulvio Alexandre
Rodrigues, Antônio Márcio
GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study
title GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study
title_full GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study
title_fullStr GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study
title_full_unstemmed GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study
title_short GABA(a) excitation and synaptogenesis after Status Epilepticus – A computational study
title_sort gaba(a) excitation and synaptogenesis after status epilepticus – a computational study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843660/
https://www.ncbi.nlm.nih.gov/pubmed/29520076
http://dx.doi.org/10.1038/s41598-018-22581-6
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