NMDA-induced response in pyramidal neurons of the rat medial prefrontal cortex slices consists of NMDA and non-NMDA components

Abstract

Using the techniques of intracellular recording, we examined and characterized the membrane response induced by N-methyl- d-aspartate (NMDA) and compared the excitatory postsynaptic potentials (EPSPs) elicited by NMDA and by electrical stimulation of the forceps minor in presumed pyramidal cells of the rat medial prefrontal cortex (mPFC) slice preparation. Bath application of NMDA produced EPSPs, membrane depolarization, and bursts of action potentials. These effects were completely blocked by the NMDA receptor antagonist d-2-amino-phosphonopentanoic acid (d-AP5). The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX) markedly decreased NMDA-induced responses and converted the I– V relationship curve of NMDA from a curvi-linear to the characteristic J-shape, thus indicating the existence of a non-NMDA component. Synaptic responses elicited by electrical stimulation of the forceps minor also consisted of NMDA and non-NMDA components. Both NMDA- and electrical stimulation-elicited EPSPs were markedly reduced or completely abolished by using Ca 2+-free artificial cerebrospinal fluid (ACSF), ACSF containing either TTX, low Ca 2+ plus Cd 2+, or a membrane permeable Ca 2+ chelator BAPTA-AM (when BAPTA was loaded in the recording electrode, it was without effect). Under these conditions, NMDA-induced depolarization was significantly reduced. Taken together, these results suggest that in addition to a direct action on pyramidal neurons, NMDA causes a release of excitatory amino acids (EAAs), which in turn activate non-NMDA receptors.