Title: Glycine binding sites of presynaptic NMDA receptors may tonically regulate glutamate release in the rat visual cortex

In the central nervous system, activation of N-methyl-D-aspartate receptor (NMDA-R) glycine binding sites is a prerequisite for activation of postsynaptic NMDA-Rs by the excitatory neurotransmitter glutamate. Here we provide electrophysiological evidence that the glycine binding sites of presynaptic NMDA-Rs regulate glutamate release in layer II/III pyramidal neurons of the rat visual cortex. Specifically, our results reveal that the frequency of miniature excitatory postsynaptic currents (mEPSCs) is significantly reduced by 7-chloro-kynurenic acid (7-Cl KYNA), a NMDA-R glycine binding site antagonist, and glycine or D-serine reverses this effect. Similar results are obtained when the open–channel NMDA receptor blocker, MK-801, is included in the recording pipette. Our data indicate that the glycine binding site of postsynaptic NMDA-Rs is not saturated. Moreover, they suggest that presynaptic NMDA-Rs are located in layer II/III pyramidal neurons of the rat visual cortex, and that the glycine binding site of presynaptic NMDA-Rs tonically regulates glutamate release.