TY - JOUR
T1 - Changes of Ionic Concentrations During Seizure Transitions — A Modeling Study
AU - Gentiletti, Damiano
AU - Suffczynski, Piotr
AU - Gnatkovsky, Vadym
AU - de Curtis, Marco
PY - 2016
Y1 - 2016
N2 - Traditionally, it is considered that neuronal synchronization in epilepsy is caused by a chain reaction of synaptic excitation. However, it has been shown that synchronous epileptiform activity may also arise without synaptic transmission. In order to investigate the respective roles of synaptic interactions and nonsynaptic mechanisms in seizure transitions, we developed a computational model of hippocampal cells, involving the extracellular space, realistic dynamics of (Formula presented.), (Formula presented.), (Formula presented.) and (Formula presented.) ions, glial uptake and extracellular diffusion mechanisms. We show that the network behavior with fixed ionic concentrations may be quite different from the neurons’ behavior when more detailed modeling of ionic dynamics is included. In particular, we show that in the extended model strong discharge of inhibitory interneurons may result in long lasting accumulation of extracellular (Formula presented.), which sustains the depolarization of the principal cells and causes their pathological discharges. This effect is not present in a reduced, purely synaptic network. These results point to the importance of nonsynaptic mechanisms in the transition to seizure.
AB - Traditionally, it is considered that neuronal synchronization in epilepsy is caused by a chain reaction of synaptic excitation. However, it has been shown that synchronous epileptiform activity may also arise without synaptic transmission. In order to investigate the respective roles of synaptic interactions and nonsynaptic mechanisms in seizure transitions, we developed a computational model of hippocampal cells, involving the extracellular space, realistic dynamics of (Formula presented.), (Formula presented.), (Formula presented.) and (Formula presented.) ions, glial uptake and extracellular diffusion mechanisms. We show that the network behavior with fixed ionic concentrations may be quite different from the neurons’ behavior when more detailed modeling of ionic dynamics is included. In particular, we show that in the extended model strong discharge of inhibitory interneurons may result in long lasting accumulation of extracellular (Formula presented.), which sustains the depolarization of the principal cells and causes their pathological discharges. This effect is not present in a reduced, purely synaptic network. These results point to the importance of nonsynaptic mechanisms in the transition to seizure.
KW - ionic dynamics
KW - modeling
KW - Potassium
KW - seizures
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U2 - 10.1142/S0129065717500046
DO - 10.1142/S0129065717500046
M3 - Article
AN - SCOPUS:84994177316
JO - International Journal of Neural Systems
JF - International Journal of Neural Systems
SN - 0129-0657
ER -