Disruption to gap junction connectivity wasĪpplied at time T = 2 seconds and is marked with Network with electrical and chemical synapses to the localized breach in D Raster plot showing the response of a model Firing rate was computed over the time window ofĢ0 seconds. Neuronal firing rate in baseline conditions (model network with fully For comparison, dashed line is the averaged Firing rate was computed over the time window Timing of lesion is marked with red line. Of lesion is parameterized by the probabilityĪ connection between a pair of model neurons in the predefined area Network to the localized lesion of gap junction connectivity. 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.Ī Raster plots showing the response of model neuronal Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. 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.
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. 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. 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. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. 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. Electrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity.
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