N-methylaspartate receptors mediate epileptiform activity evoked in some, but not all, conditions in rat neocortical slices

Abstract

Using intracellular recordings from pyramidal neurons in isolated slices of rat cerebral cortex epileptiform discharges evoked (1) in the presence of γ-aminobutyric acid antagonists, and (2) in the absence of Mg 2+ were compared. Depolarization shift responses recorded in the presence of bath applied picrotoxin, or electrophoretically applied picrotoxin or bicuculline, were similar in many respects to depolarization shifts reported previously, except that they could be evoked by stimuli subthreshold for evoking discernible postsynaptic potentials in these experiments. Large depolarizations evoked by repetitive activation of an N-methylaspartate receptor mediated synapse in the absence of Mg 2+, displayed several properties similar to those of depolarization shifts evoked in the presence of γ-aminobutyric acid antagonists, i.e. similar shape, latency, inability to follow high repetition rates and a similar voltage relation, suggesting activation of the same cellular mechanism. “Slow spikes” evoked as part of the response to electrophoretically applied N-methylaspartate were augmented, i.e. they were replaced by larger, longer, more complex events, when γ-aminobutyric acid antagonists were applied. The potentiated response, evoked in the absence of Mg 2+, was dependent on the activation of an N-methylaspartate receptor mediated synapse and was blocked by N-methylaspartate antagonists. In contrast, depolarization shifts could be evoked in the presence of large doses of N-methylaspartate antagonists, when γ-aminobutyric acid antagonists were applied. Spontaneous depolarizations similar to depolarization shifts were recorded when cells were exposed to low, tonic, electrophoretic applications of excitatory amino acids under control conditions. In addition, some potentiation of the N-methylaspartate receptor mediated excitatory postsynaptic potential was achieved in the presence of Mg 2+ when cells were depolarized by 10–20mV. Depolarization shifts evoked when bicuculline was applied electrophoretically to different parts of the dendritic field, some hundreds of microns from the soma, differed in shape, latency and time course and the depolarization shift evoked when bicuculline was applied at one site summed with the depolarization shift evoked when it was applied elsewhere. We conclude that different inputs are required to activate the responses evoked in the presence of γ-aminobutyric acid antagonists and in the absence of Mg 2+. The possibility that both involve activation of dendritic Ca 2+currents and that the magnitude of the response depends on the proportion of the dendritic field activated, is discussed.