Study on the mechanisms of seizure-like events suppression effect by electrical stimulation using a microelectrode array

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Abstract

In this paper, we studied the mechanisms underlying the suppression of seizure-like events (SLEs) by electrical stimulation. We conducted an in-vitro experiment using entorhinal cortex combined hippocampal slices and two convulsant drugs, bicuculline and 4-aminopyridine, to induce spontaneous SLEs. We used a microelectrode array to observe network dynamics over the entire hippocampal area simultaneously, including regions far from the stimulation site. We stimulated the entorhinal cortex region, which has been determined to be a focus of SLEs by Granger causality analysis of multichannel time series data, by an external electrode. In bicuculline application, electrical stimulation showed a marked suppression effect, even though the sizes of the effective region differed. In 4-aminopyridine application, however, stimulation under the same conditions did not suppress the activities in ∼80% of SLEs. The suppression effect was more remarkable in the areas surrounding the stimulation site in both cases. Our experimental results could support the neuronal depolarization blockade mechanism by accumulation of extracellular potassium ions, which is one of the most convincing mechanisms to understand seizure suppression phenomena because of electrical stimulation. Computer simulation using a neuronal network model also confirmed the mechanism.

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