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The Journal of Neuroscience, September 15, 2000, 20(18):6820-6829

Ictal Epileptiform Activity Is Facilitated by Hippocampal GABAA Receptor-Mediated Oscillations

Rüdiger Köhling1, 2, Martin Vreugdenhil1, Enrico Bracci1, and John G. R. Jefferys1

1 Division of Neuroscience (Neurophysiology), The Medical School, The University of Birmingham, Birmingham B15 2TT, United Kingdom, and 2 Institut für Physiologie, Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany

The cellular and network mechanisms of the transition of brief interictal discharges to prolonged seizures are a crucial issue in epilepsy. Here we used hippocampal slices exposed to ACSF containing 0 Mg2+ to explore mechanisms for the transition to prolonged (3-42 sec) seizure-like ("ictal") discharges. Epileptiform activity, evoked by Shaffer collateral stimulation, triggered prolonged bursts in CA1, in 50-60% of slices, from both adult and young (postnatal day 13-21) rats. In these cases the first component of the CA1 epileptiform burst was followed by a train of population spikes at frequencies in the gamma  band and above (30-120 Hz, reminiscent of tetanically evoked gamma  oscillations). The gamma  burst in turn could be followed by slower repetitive "tertiary" bursts. Intracellular recordings from CA1 during the gamma  phase revealed long depolarizations, action potentials rising from brief apparent hyperpolarizations, and a drop of input resistance. The CA1 gamma  rhythm was completely blocked by bicuculline (10-50 µM), by ethoxyzolamide (100 µM), and strongly attenuated in hyperosmolar perfusate (50 mM sucrose). Subsequent tertiary bursts were also blocked by bicuculline, ethoxyzolamide, and in hyperosmolar perfusate. In all these cases intracellular recordings from CA3 revealed only short depolarizations. We conclude that under epileptogenic conditions, gamma  band oscillations arise from GABAAergic depolarizations and that this activity may lead to the generation of ictal discharges.

Key words: depolarizing GABA response; neuronal synchronization; gamma rhythms; ictogenesis; epilepsy models; hippocampus

Copyright © 2000 Society for Neuroscience  0270-6474/00/20186820-10$05.00/0


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