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Modeling of seizure transitions with ion concentration dynamics
BMC Neuroscience volume 16, Article number: P242 (2015)
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 . 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 . 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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De Curtis M, Gnatkovsky V: Reevaluating the mechanisms of focal ictogenesis: the role of low-voltage fast activity. Epilepsia. 2009, 50 (12): 2514-2525.
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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). https://doi.org/10.1186/1471-2202-16-S1-P242
- Inhibitory Interneuron
- Extracellular Potassium
- Neuronal Coupling
- Realistic Dynamic
- Synaptic Coupling