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

Field potential and intracellular recordings were made in slices of human n eocortical tissue obtained during surgery for the treatment of seizures ass ociated with focal cortical dysplasia. Ictal-like epileptiform discharges, along with isolated field potentials, were induced by bath application of 4 -aminopyridine (50-100 mu M). Some of the isolated field potentials were as sociated with fast transients representing population spikes. Field potenti al profile analysis indicated that both types of synchronous activity had m aximal negative values at 1,400 to 1,600 mu m from the pia. The intracellul ar counterpart of the ictal-like discharge was a prolonged membrane depolar ization capped by repetitive action potential burst firing. By contrast, th e isolated field potentials were mirrored by long-lasting depolarizations w ith minimal action potential firing; only when population spikes occurred, the isolated field potentials were associated with epileptiform action pote ntial bursting. Ictal-like discharges were abolished by either N-methyl-D-a spartate or non-N-methyl-D-aspartate receptor antagonists. In contrast, the isolated field potentials continued to occur synchronously during excitato ry transmission blockade (although they lacked fast transients) but were ab olished by the gamma-aminobutyric acid(A) receptor antagonist bicuculline m ethiodide (n = 2 slices). Our study demonstrates that focal cortical dyspla sia tissue maintained in vitro has an intrinsic ability to generate ictal-l ike epileptiform events when challenged with 4-aminopyridine. These dischar ges depend on excitatory amino acid receptor-mediated mechanisms. Our resul ts also show the presence in focal cortical dysplasia tissue of glutamaterg ic-independent synchronous potentials that are mainly contributed by gamma- aminobutyric acid(A) receptor-mediated conductances.