Neurosteroids differentially modulate fast and slow interictal discharges in the hippocampal CA3 area.

Two types of spontaneous interictal discharge, identified as fast and slow events, can be recorded from the hippocampal CA3 area in rat brain slices during application of 4-aminopyridine (4AP) (50 μm). Here, we addressed how neurosteroids modulate the occurrence of these interictal events and of the associated high-frequency oscillations (HFOs) (ripples, 80-200 Hz; fast ripples, 250-500 Hz). Under control conditions (i.e. during 4AP application), ripples and fast ripples were detected in 12.3 and 17.5% of fast events, respectively; in contrast, the majority of slow events (> 98%) did not co-occur with HFOs. Application of 0.1, 1 or 5 μm allotetrahydrodeoxycorticosterone (THDOC) to 4AP-treated slices caused a dose-dependent decrease in the duration of the fast events and an increase in the occurrence of ripples, but not fast ripples; in contrast, the duration of slow events increased. THDOC potentiated the slow events that were recorded during pharmacological blockade of glutamatergic transmission, but had no effect on interictal discharges occurring during GABAA receptor antagonism. These results demonstrate that potentiation of GABAA receptor-mediated signaling by THDOC differentially affects slow and fast interictal discharges; these differences may provide insights into how hyperexcitable activity is influenced by neurosteroids.