Region-specific modulation and predictive potential of the oscillatory dynamics in an ex vivo model of ictogenesis in the CA1, CA3 and dentate gyrus

Abstract

The hippocampus, including the cornu ammonis (CA) and dentate gyrus (DG) subregions, is a brain area highly susceptible to seizure-like activity (SLA). Most studies conducted in vivo have been performed in a single hippocampal subregion. In our study, we used the high [K+] (HK+) model of SLA to investigate the role of oscillatory activity in predicting SLA and in its modulation by anti-epileptic drugs in the three hippocampal subregions (CA1, CA3 and DG). For this, we recorded spontaneous local field potentials (LFPs) in CA1, CA3 and DG subregions from mouse hippocampal slices. We find that the oscillatory activity in the 20 second pre-ictal period is significantly different compared to the oscillatory activity in the absence of SLA or to a more distant period from the ictal event. A classification algorithm revealed that the oscillatory dynamics, particularly in the CA1 subregion, can predict the emergence of an ictal event with high accuracy. Furthermore, oscillatory activity is differentially modulated by anti-epileptic drugs in the different hippocampal subregions. We found that diazepam and carbamazepine modulated the oscillatory activity significantly greater in the CA3 and DG subregions, compared to CA1. Imaging of neuronal activation in the ex vivo model of seizure-like activity, using the Fos protein as an activity marker, revealed a similar subregion-dependent differential modulation following diazepam and carbamazepine perfusion. Therefore, while oscillatory activity in the pre-ictal period in the CA1 subregion can better predict the emergence of ictal events, anti-convulsant drugs have a stronger effect in oscillatory activity in the CA3 and DG subregions.