Involvement of the intracellular Ca 2+/calmodulin kinase activation network in the induction of bicuculline-induced epileptic discharges in hippocampal slices, and the brain informatics simulator “HIPPO-STATION”

Abstract

The effects of Ca 2+/calmodulin kinase II inhibitor on bicuculline-induced epileptic discharges (BIED) in guinea-pig hippocampal slices were studied. The epileptic discharges were recorded from transverse guinea-pig hippocampal slices (4–500 μm thick) when bicuculline, a GABAa receptor antagonist, was applied to the slices. The results were as follows: (1) More than 5 μM bicuculline could induce epileptic discharges. (2) The epileptic discharges were also seen even from the isolated CA3 slices. (3) AP5, an NMDA receptor antagonist, decreased the frequency of the epileptic discharges. (4) KN-93, a CaMKII inhibitor, also significantly decreased the frequency of the discharges, while KN-92, a negative control of KN-93, did not. NMDA receptor and CaMKII play important roles in the induction of long-term synaptic change in the hippocampus. Our results therefore suggest that the long-term synaptic change in the CA3 region can modulate the frequency of bicuculline-induced epileptic discharges in hippocampal slices. In order to simulate this model, we are developing the generalized brain simulator HIPPO-STATION.