Direct demonstration of an N-methyl-D-aspartate receptor mediated component of excitatory synaptic transmission in area CA1 of the rat hippocampus.

The action of a new non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), on synaptic transmission in area CA1 of the rat hippocampus has been examined. Intracellular and extracellular recordings showed CNQX to be a potent antagonist of synaptic potentials evoked by stimulation of the Schaffer collateral-commissural fibre system. One to 2 microM CNQX was sufficient to reduce the excitatory postsynaptic potential (EPSP) by 50%. CNQX is therefore about 100 times more potent than previously available non-NMDA receptor antagonists. In the presence of CNQX, a small depolarizing potential could still be evoked. This potential was sensitive to the NMDA-receptor blocker, 2-amino-5-phosphonovaleric acid (APV), increased in size on depolarizing the neurone and also increased in size on removing Mg2+ from the perfusing medium. This residual EPSP therefore has characteristics which are consistent with its mediation via the NMDA receptor-coupled ionophore. These results indicate a dual composition of the monosynaptic excitatory potential in area CA1.