The induction and modification of voltage-sensitive responses in cat neocortical nuerons by N-methyl- d-aspartate

Abstract

The actions of the excitatory amino acid, N-methyl- d-aspartate (NMDA), on layer V neurons of cat sensorimotor cortex were examined in an in vitro slice preparation using current clamp, single electrode voltage clamp (SEVC), and ionic substitution techniques. Low doses of NMDA evoked a slow depolarization with a net decrease of input conductance. Larger doses additionally evoked repetitive firing rhythmic depolarization shifts (DSs), low-threshold calcium spikes (in the presence of TEA+) and bistable membrane potential behavior. Ionic substitution experiments suggested that entry of both Ca + and Na + ions contributed to the NMDA responses. Attention was focused on the NMDA response with Ca 2+ entry blocked. Examination by SEVC revealed that, in both normal cells and in the presence of several blocking agents, NMDA induced a highly voltage-dependent inward ionic current which would could result in a region of negative slope conductance on the cell's current-voltage relation. The development of this current seems capable of accounting for all aspects of the observed response, including the Dss and low-threshold Ca 2+ spikes, Substitution of TEA + for most external Na + (with Ca 2+ entry blocked) largely eliminated the NMDA responses and corresponding ionic current. Our results in neocortical neurons are compared to those recently obtained in cultured murine neurons.