Epileptiform discharges in the human dysplastic neocortex: In vitro physiology and pharmacology

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Abstract
Field potential and intracellular recordings were made in slices of human neocortical tissue obtained during surgery for the treatment of seizures associated with focal cortical dysplasia. Ictal‐like epileptiform discharges, along with isolated field potentials, were induced by bath application of 4‐aminopyridine (50–100 μM). Some of the isolated field potentials were associated with fast transients representing population spikes. Field potential profile analysis indicated that both types of synchronous activity had maximal negative values at 1,400 to 1,600 μm from the pia. The intracellular counterpart of the ictal‐like discharge was a prolonged membrane depolarization capped by repetitive action potential burst firing. By contrast, the isolated field potentials were mirrored by long‐lasting depolarizations with minimal action potential firing; only when population spikes occurred, the isolated field potentials were associated with epileptiform action potential bursting. Ictal‐like discharges were abolished by either N‐methyl‐D‐aspartate or non–N‐methyl‐D‐aspartate receptor antagonists. In contrast, the isolated field potentials continued to occur synchronously during excitatory transmission blockade (although they lacked fast transients) but were abolished by the γ‐aminobutyric acidA receptor antagonist bicuculline methiodide (n = 2 slices). Our study demonstrates that focal cortical dysplasia tissue maintained in vitro has an intrinsic ability to generate ictal‐like epileptiform events when challenged with 4‐aminopyridine. These discharges depend on excitatory amino acid receptor–mediated mechanisms. Our results also show the presence in focal cortical dysplasia tissue of glutamatergic‐independent synchronous potentials that are mainly contributed by γ‐aminobutyric acidA receptor–mediated conductances.