Role of excitatory amino acid receptors in synaptic transmission in area CA1 of rat hippocampus

The new antagonist 6-cyano-7-nitroquinoxaline-2.3-dione (CNQX). which blocks responses to kainate and quisqualate, has been used in conjunction with D-2-amino-5-phosphonovalerate (APV), which blocks selectively responses to N-methyl-D-aspartate (NMDA). to determine the role of excitatory amino acid receptors in synaptic transmission. An excitatory postsynaptic potential (EPSP) - inhibitory postsynaptic potential (IPSP) sequence was evoked in CA1 neurons by stimulation of the Schaffer collateral-commissural pathway in rat hippocampal slices. CNQX (10 $\mu$ M) substantially reduced the EPSP without having any effect on input resistance or membrane potential. The IPSP was also reduced provided that the stimulating electrode was place approximately 1 mm from the recording electrode. The EPSP that remained in the presence of CNQX had characteristics of an NMDA receptor-mediated potential it had a slow timecourse, summated at high frequencies, was blocked reversibly by APV increased greatly in size in Mg$^{2+}$-free medium, and showed an anomalous voltage dependence in Mg$^{2+}$-containing medium. In the presence of CNQX, an APV-sensitive polysynaptic GABAergic IPSP could be evoked, indicating that NMDA receptors can mediate suprathreshold EPSPS in inhibitory interneurons. It is suggested that either NMDA or non-NMDA receptors can, under different circumstances, mediate the synaptic excitation of pyramidal neurons and inhibitory interneurons in area CA1 of the hippocampus.