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Fast activity at seizure onset is mediated by inhibitory circuits in the entorhinal cortex in vitro
Author(s) -
Gnatkovsky Vadym,
Librizzi Laura,
Trombin Federica,
de Curtis Marco
Publication year - 2008
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21519
Subject(s) - ictal , neuroscience , entorhinal cortex , inhibitory postsynaptic potential , bursting , electrophysiology , depolarization , epilepsy , postsynaptic potential , excitatory postsynaptic potential , temporal lobe , interneuron , epileptogenesis , chemistry , biology , hippocampus , medicine , biophysics , receptor
Objective Network mechanisms responsible for focal seizure initiation are still largely unknown. One of the prevalent seizure patterns observed during diagnostic intracranial recordings performed in patients with mesial temporal lobe epilepsy is characterized by fast activity at 20 to 30Hz. We reproduced 20 to 30Hz oscillations at seizure onset in the temporal lobe of the in vitro isolated guinea pig brain to study cellular and network mechanisms involved in its generation. Methods Seizure‐like activity was induced in the isolated brain by 3‐minute arterial perfusion of 50μM bicuculline. Intracellular, extracellular, and ion‐selective electrophysiological recordings were performed simultaneously in the entorhinal cortex (EC) during interictal‐ictal transition. Results Principal neurons in deep and superficial layers of the EC did not generate action potentials during fast activity at ictal onset, whereas sustained firing was observed in putative interneurons. Within 5 to 10 seconds from seizure initiation, principal neurons generated a prominent firing that correlated with the appearance of extracellular hypersynchronous bursting discharges. In superficial neurons, fast activity correlated with rhythmic IPSPs that progressively decreased in amplitude during the development of a slow depolarization associated with an increase in extracellular potassium. Interpretation We conclude that in an acute model of temporal lobe ictogenesis, sustained inhibition without firing of EC principal neurons correlates with the onset of a focal seizure. The progression of the ictal discharge is contributed by a potassium‐dependent change in reversal potential of inhibitory postsynaptic potentials. These findings demonstrate a prominent role of inhibitory networks during the transition to seizure in the EC. Ann Neurol 2008;64:674–686