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A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity
The early cellular events that in a brain network lead to seizure generation and govern seizure propagation are probably based on different cellular mechanisms. Experimental models in which these events can be separately studied would contribute to improve our understanding of epilepsy. We recently...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier/North-Holland Biomedical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751973/ https://www.ncbi.nlm.nih.gov/pubmed/25863141 http://dx.doi.org/10.1016/j.jneumeth.2015.04.001 |
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author | Losi, Gabriele Marcon, Iacopo Mariotti, Letizia Sessolo, Michele Chiavegato, Angela Carmignoto, Giorgio |
author_facet | Losi, Gabriele Marcon, Iacopo Mariotti, Letizia Sessolo, Michele Chiavegato, Angela Carmignoto, Giorgio |
author_sort | Losi, Gabriele |
collection | PubMed |
description | The early cellular events that in a brain network lead to seizure generation and govern seizure propagation are probably based on different cellular mechanisms. Experimental models in which these events can be separately studied would contribute to improve our understanding of epilepsy. We recently described an in vitro model in entorhinal cortex slices from young rats in which focal seizure-like discharges (SLDs) can be induced in spatially defined regions and at predictable times by local NMDA applications performed in the presence of 4-amimopyridine (4-AP) and low extracellular Mg(2+). Through the use of single-dual cell patch-clamp and field potential recordings, and Ca(2+) imaging from large ensembles of neurons, interneurons and astrocytes, we here extend this model to entorhinal and temporal cortex slices of rat and mouse brain, providing evidence that multiple SLDs exhibiting the typical tonic–clonic discharge pattern can be also evoked in these cortical regions by successive NMDA applications. Importantly, the temporal cortex is more accessible to viral vector injections than the entorhinal cortex: this makes it feasible in the former region the selective expression in inhibitory interneurons or principal neurons of genetically encoded Ca(2+) indicators (GECI) or light-gated opsins. In this model, an optogenetic approach allows to activate specific neuronal types at spatially defined locations, i.e., the focus or the propagating region, and at precise time, i.e., before or during SLD. The NMDA/4-AP model can, therefore, represent a valuable tool to gain insights into the role of specific cell populations in seizure generation, propagation and cessation. |
format | Online Article Text |
id | pubmed-4751973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier/North-Holland Biomedical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47519732016-03-02 A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity Losi, Gabriele Marcon, Iacopo Mariotti, Letizia Sessolo, Michele Chiavegato, Angela Carmignoto, Giorgio J Neurosci Methods Basic Neuroscience The early cellular events that in a brain network lead to seizure generation and govern seizure propagation are probably based on different cellular mechanisms. Experimental models in which these events can be separately studied would contribute to improve our understanding of epilepsy. We recently described an in vitro model in entorhinal cortex slices from young rats in which focal seizure-like discharges (SLDs) can be induced in spatially defined regions and at predictable times by local NMDA applications performed in the presence of 4-amimopyridine (4-AP) and low extracellular Mg(2+). Through the use of single-dual cell patch-clamp and field potential recordings, and Ca(2+) imaging from large ensembles of neurons, interneurons and astrocytes, we here extend this model to entorhinal and temporal cortex slices of rat and mouse brain, providing evidence that multiple SLDs exhibiting the typical tonic–clonic discharge pattern can be also evoked in these cortical regions by successive NMDA applications. Importantly, the temporal cortex is more accessible to viral vector injections than the entorhinal cortex: this makes it feasible in the former region the selective expression in inhibitory interneurons or principal neurons of genetically encoded Ca(2+) indicators (GECI) or light-gated opsins. In this model, an optogenetic approach allows to activate specific neuronal types at spatially defined locations, i.e., the focus or the propagating region, and at precise time, i.e., before or during SLD. The NMDA/4-AP model can, therefore, represent a valuable tool to gain insights into the role of specific cell populations in seizure generation, propagation and cessation. Elsevier/North-Holland Biomedical Press 2016-02-15 /pmc/articles/PMC4751973/ /pubmed/25863141 http://dx.doi.org/10.1016/j.jneumeth.2015.04.001 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Basic Neuroscience Losi, Gabriele Marcon, Iacopo Mariotti, Letizia Sessolo, Michele Chiavegato, Angela Carmignoto, Giorgio A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity |
title | A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity |
title_full | A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity |
title_fullStr | A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity |
title_full_unstemmed | A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity |
title_short | A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity |
title_sort | brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity |
topic | Basic Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751973/ https://www.ncbi.nlm.nih.gov/pubmed/25863141 http://dx.doi.org/10.1016/j.jneumeth.2015.04.001 |
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