Activation of the NMDA receptor: a correlate in the dentate gyrus field potential and its relationship to long-term potentiation and kindling

Abstract

Stimulation trains, but not stimulation pulses, are capable of inducing long-term potentiation (LTP). In this paper we report experiments designed to examine, in chronic preparations, the characteristics of a component unique to the train-evoked response. Stimulation trains applied to the perforant path evoked population EPSP's and population spikes in the dentate gyrus that were nearly identical to those evoked by single pulses of comparable intensity. The trains also triggered a prolonged potential, negative at the dendritic pole of our electrodes, which far outlasted the pulse-evoked response. We substracted pulse-evoked responses from these train-evoked responses which left us with a waveform that peaked at about 15 ms and lasted for about 50–70 ms. The GABA agonists, diazepam and sodium pentobarbital, had no significant effect on this component, but the NMDA antagonists, ketamine and MK-801, both depressed it by over 30%. The late component had a very low threshold, which might account for the frequent observation of LTP induction at very low thresholds. Also, the late component is reliably seen in all animals showing LTP, even in the occasional animals that show no population spikes. The late component did not appear to be affected by the induction of LTP, and was either not affected or was depressed following the completion of kindling. When the ‘NMDA-component’ of the train-evoked response was monitored, along with LTP, in an ascending intensity train series, it was found that both the NMDA-component and the LTP increased smoothly. There was no sudden appearance of the NMDA-component at the LTP threshold. The presence of an NMDA component in the field potential of the chronic preparation allows the monitoring of the levels of NMDA activation over prolonged periods.