1Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
2Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

Abstract 

The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we
investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K+ concentration (8.5 mmol/L) in the bath, and
the effects of the anti-epileptic drug valproate (VPA) on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a–b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration (100 μmol/L) suppressed the propagation speed but not the rate or duration of high-K+-induced discharges. Our findings suggest
that pacemakers exist in the CA3a–b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges
in the network by reducing the propagation speed.

Keywords

epileptiform discharges; hippocampal slices; microelectrode array; valproate

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