Characterizing Concentration-Dependent Neural Dynamics of 4-Aminopyridine-Induced Epileptiform Activity

Abstract

studies varies from 3 μM to 40 mM. Here, we explored the effects of various 4AP concentrations on the development and characteristics of hippocampal epileptiform activity in acute mouse brain slices of either sex. Using multi-electrode array recordings, we show that 4AP induces hippocampal epileptiform activity for a broad range of concentrations. The frequency component and the spatiotemporal patterns of the epileptiform activity revealed a dose-dependent response. Finally, in the presence of 4AP, reduction of KCC2 co-transporter activity by KCC2 antagonist VU0240551 prevented the manifestation of the frequency component differences between different concentrations of 4AP. Overall, the study predicts that different concentrations of 4AP can result in the different mechanisms behind hippocampal epileptiform activity, of which some are dependent on the KCC2 co-transporter function.