Gap junctions and epileptic seizures--two sides of the same coin?

Electrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses pro...

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Main Authors: Vladislav Volman, Matjaž Perc, Maxim Bazhenov
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3105095?pdf=render
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author Vladislav Volman
Matjaž Perc
Maxim Bazhenov
author_facet Vladislav Volman
Matjaž Perc
Maxim Bazhenov
author_sort Vladislav Volman
collection DOAJ
description Electrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic), some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. Here we used a computational modeling approach to address the role of neuronal gap junctions in shaping the stability of a network to perturbations that are often associated with the onset of epileptic seizures. We show that under some circumstances, the addition of gap junctions can increase the dynamical stability of a network and thus suppress the collective electrical activity associated with seizures. This implies that the experimentally observed post-seizure additions of gap junctions could serve to prevent further escalations, suggesting furthermore that they are a consequence of an adaptive response of the neuronal network to the pathological activity. However, if the seizures are strong and persistent, our model predicts the existence of a critical tipping point after which additional gap junctions no longer suppress but strongly facilitate the escalation of epileptic seizures. Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. Which dynamic scenario (seizure suppression or seizure escalation) is ultimately adopted by the network depends critically on the strength and duration of seizures, in turn emphasizing the importance of temporal and causal aspects when linking gap junctions with epilepsy.
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spelling doaj.art-5f75297ee12241b88a716522c06ccc012022-12-22T00:11:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e2057210.1371/journal.pone.0020572Gap junctions and epileptic seizures--two sides of the same coin?Vladislav VolmanMatjaž PercMaxim BazhenovElectrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic), some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. Here we used a computational modeling approach to address the role of neuronal gap junctions in shaping the stability of a network to perturbations that are often associated with the onset of epileptic seizures. We show that under some circumstances, the addition of gap junctions can increase the dynamical stability of a network and thus suppress the collective electrical activity associated with seizures. This implies that the experimentally observed post-seizure additions of gap junctions could serve to prevent further escalations, suggesting furthermore that they are a consequence of an adaptive response of the neuronal network to the pathological activity. However, if the seizures are strong and persistent, our model predicts the existence of a critical tipping point after which additional gap junctions no longer suppress but strongly facilitate the escalation of epileptic seizures. Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. Which dynamic scenario (seizure suppression or seizure escalation) is ultimately adopted by the network depends critically on the strength and duration of seizures, in turn emphasizing the importance of temporal and causal aspects when linking gap junctions with epilepsy.http://europepmc.org/articles/PMC3105095?pdf=render
spellingShingle Vladislav Volman
Matjaž Perc
Maxim Bazhenov
Gap junctions and epileptic seizures--two sides of the same coin?
PLoS ONE
title Gap junctions and epileptic seizures--two sides of the same coin?
title_full Gap junctions and epileptic seizures--two sides of the same coin?
title_fullStr Gap junctions and epileptic seizures--two sides of the same coin?
title_full_unstemmed Gap junctions and epileptic seizures--two sides of the same coin?
title_short Gap junctions and epileptic seizures--two sides of the same coin?
title_sort gap junctions and epileptic seizures two sides of the same coin
url http://europepmc.org/articles/PMC3105095?pdf=render
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