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Neurosteroids differentially modulate fast and slow interictal discharges in the hippocampal CA 3 area
Author(s) -
Herrington Rochelle,
Lévesque Maxime,
Avoli Massimo
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12797
Subject(s) - hippocampal formation , glutamatergic , ictal , neuroscience , neuroactive steroid , long term potentiation , chemistry , hippocampus , gabaa receptor , neurotransmission , medicine , endocrinology , receptor , biology , glutamate receptor , electroencephalography
Abstract 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.