Neurosteroids differentially modulate fast and slow interictal discharges in the hippocampal CA 3 area

Two types of spontaneous interictal discharge, identified as fast and slow events, can be recorded from the hippocampal CA 3 area in rat brain slices during application of 4‐aminopyridine (4 AP ) (50 μ m ). Here, we addressed how neurosteroids modulate the occurrence of these interictal events and of the associated high‐frequency oscillations ( HFO s) (ripples, 80–200 Hz; fast ripples, 250–500 Hz). Under control conditions (i.e. during 4 AP 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 HFO s. Application of 0.1, 1 or 5 μ m allotetrahydrodeoxycorticosterone ( THDOC ) to 4 AP ‐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 GABA A receptor antagonism. These results demonstrate that potentiation of GABA A 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.