Pharmacological Isolation and Characterization of NMDA Receptor-Mediated Synaptic Potential in the Dentate Gyrus of Rat Hippocampal Slices

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We attempted to observe the dentate gyrus field potential evoked by low-frequency stimulation of the perforant path in Mg²⁺-free medium and identify the N-methyl-D-aspartate (NMDA)receptormediated synaptic potential using rat hippocampal slices. When perfusing solution was changed from normal medium (1.3 mM Mg²⁺)to Mg²⁺-free medium, the evoked potential was greatly increased and secondary population spikes appeared following a primary population spike. The evoked potential recorded in Mg²⁺-free medium was only partly blocked by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), a nonNMDA receptor antagonist. The CNQX-resistant component of the evoked potential in Mg²⁺-free medium was completely abolished by 30 μM DL-2-amino-5-phosphonovalerate, a NMDA receptor antagonist, indicating that the NMDA receptor-mediated synaptic response can be isolated by masking the non-NMDA receptor-mediated component of the evoked potential under the Mg²⁺-free condition. The isolated NMDA receptor-mediated synaptic potential was also blocked by 7-chlorokynurenate, an antagonist at the glycine site of the NMDA receptor, and restored by the concomitant presence of glycine. Observation of pharmacologically isolated NMDA receptor-mediated synaptic potential is a simple and good method for studying the direct effects of drugs on NMDA receptor-mediated responses.