THE RELATIVE CONTRIBUTION OF NMDA RECEPTOR CHANNELS IN THE EXPRESSION OF LONG-TERM POTENTIATION IN THE HIPPOCAMPAL CA1 REGION

Long-term potentiation (LTP) was studied in the hippocampal CA1 region of guinea-pigs using a solution containing 0.1 mM magnesium and 10-mu-M of the non-N-methyl-D-aspartate (non-NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), leaving an NMDA-mediated field excitatory postsynaptic potential (EPSP). Brief high-frequency afferent tetanization induced a substantial synapse-specific potentiation of the NMDA EPSP with a time course closely resembling that previously described for LTP of the non-NMDA-mediated EPSP. This NMDA EPSP potentiation was occluded by prior induction of LTP in normal solution. Using a solution containing 0.1 mM magnesium and 1-mu-M CNQX, the EPSP was composed of both a non-NMDA- and an NMDA-mediated component which could be measured separately and in parallel. Manipulations that cause increased transmitter release, such as phorbol ester application and changes in stimulation frequency, enhanced the two measures nearly equally. Afferent tetanization induced an increase of both EPSP components, with a similar time course, the NMDA component showing a relative increase of about one-third of that of the non-NMDA one. These results suggest that, to the extent that LTP is based on an increased release of transmitter, the mechanism exhibits features distinct from those underlying other forms of enhanced release.