title: Ictal epileptiform activity is facilitated by hippocampal GABAA receptor-mediated oscillations.
abstract: 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 Mg(2+) 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 microm), by ethoxyzolamide (100 microm), 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 GABA(A)ergic depolarizations and that this activity may lead to the generation of ictal discharges.
authors.affiliation: Division of Neuroscience (Neurophysiology), The Medical School, The University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Köhling
authors.forename: M
authors.initials: M
authors.lastname: Vreugdenhil
authors.forename: E
authors.initials: E
authors.lastname: Bracci
authors.forename: J G
authors.initials: JG
authors.lastname: Jefferys
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011930:Reaction Time; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D008274:Magnesium