Effect of External Perturbations on Seizure Dynamics - in Vitro Results and Computational Modelling

0489116 - ÚI 2019 US eng A - Abstract
Hlinka, Jaroslav - Chang, W.C. - Paluš, Milan - Jefferys, J. G. R. - Jiruška, Přemysl
Effect of External Perturbations on Seizure Dynamics - in Vitro Results and Computational Modelling.
Epilepsia. Wiley. Roč. 57, suppl. 2 (2016), s. 44-44. ISSN 0013-9580. E-ISSN 1528-1167.
[European Congress on Epileptology /12./. 11.09.2016-15.09.2016, Prague]
Institutional support: RVO:67985807 ; RVO:67985823
Keywords : in vitro * seizure * epilepsy * computational modelling
OECD category: Neurosciences (including psychophysiology

PURPOSE: Understanding of the mechanisms of transition to seizures represents key prerequisite for their successful control. Previously we have demonstrated in vitro that seizures are preceded by detectable changes in neuronal and network dynamics. In the current study we have examined how the excitatory input can modify the transition to seizures. METHOD: The experiments were performed in vitro in rat hippocampal slices perfused with artificial CSF containing high potassium (>8 mM). Field potentials from the hippocampal CA1 and CA3 regions were recorded using multiple extracellular electrodes. To study the effect of CA3 activity on CA1, further measurements were taken from isolated CA1 slices. RESULTS: Spontaneous seizure-like events were generated within the CA1 region with a mean inter-seizure interval of 60.4 4.4 s. Seizures did not occur abruptly, but were preceded by a progressive buildup of high-frequency activity at 200 Hz. The CA3 region generated interictal discharges propagating to CA1 and interfering with the high-frequency activity. Recorded data motivated a minimal mathematical model, with state space defined by mean firing rate and excitability. For intermediate excitability, model contains a bistability of low-firing rate and high-firing rate state. Slow excitability dynamics lead to emergence of cyclic regime shifts between the two states. However, random noise or external perturbation also affect state switching. Simulations demonstrate that during stable part of the interictal period excitatory input reversed transition to seizure, while in low stability states it could induce seizure. CONCLUSION: This study demonstrates the dual nature of the effect of excitatory synaptic on input seizure initiation. The impact of the excitatory perturbation depended on the spontaneously slowly changing state of the system. These observation represent plausible explanation for dual, both proconvulsive and anticonvulsive, effect of interictal epileptiform activity.
Permanent Link: http://hdl.handle.net/11104/0283589