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Modeling of seizure transitions with ion concentration dynamics

Traditionally it is considered that neuronal synchronization in epilepsy is caused by a chain reaction of synaptic excitation. However, it has been shown that synaptic transmission is not necessary for epileptiform synchronization [1]. In order to investigate the respective roles of synaptic and non-synaptic neuronal coupling in seizure transitions, we developed a computational model of hippocampal network, involving extracellular space, realistic dynamics of Na+, K+ and Cl- ions, the glial uptake and diffusion mechanism. We show that network behavior under synaptic coupling conditions may be quite different from the neurons' activities when specific non-synaptic components are included. In particular, we show that in the extended model, strong discharge of inhibitory interneurons may result in long lasting accumulation of extracellular K+, which sustains depolarization of principal cells and causes their pathological discharges. This effect is not present in a reduced, purely synaptic network. These results confirm the experimental hypothesis that increase of inhibitory interneurons firing may lead to increased firing in the pyramidal cells through accumulation of extracellular potassium [2]. The model also shows that all potassium clearance mechanisms (glial uptake, sodium-potassium pump, potassium diffusion) are critically important to reproduce the experimental findings. This means that computational modeling of seizure activity without ion dynamics may lead to unrealistic results.


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Correspondence to Damiano Gentiletti.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Gentiletti, D., De Curtis, M., Gnatkovski, V. et al. Modeling of seizure transitions with ion concentration dynamics. BMC Neurosci 16, P242 (2015).

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  • Inhibitory Interneuron
  • Extracellular Potassium
  • Neuronal Coupling
  • Realistic Dynamic
  • Synaptic Coupling