Glycine Binding Sites of Presynaptic NMDA Receptors May Tonically Regulate Glutamate Release in the Rat Visual Cortex

Abstract

In the CNS, 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 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.

Intraperiaqueductal Gray Glycine and d-Serine Exert Dual Effects on Rostral Ventromedial Medulla on- and off-Cell Activity and Thermoceptive Threshold in the Rat

“…Consistent with other previous studies (Berrino et al 1993;Li and Han 2007;Sjöström et al 2003), these data suggest that the physiological level of glycine in the PAG might be in a critical range, allowing the stimulation of a share of nonsaturated NMDARs in vivo. Indeed, considering that the EC 50 s of D-serine or glycine for NR1-NR2A (postsynaptic) receptors are known to be higher than those for NR1-NR2B (presynaptic) ones (Kew et al 1998;Kutsuwada et al 1992), one could suppose that the postsynaptic (containing NR2A) nonsaturated NMDA subtype receptors would mainly be recruited in vivo by microinjecting glycine or D-serine into the PAG.…”

Developmental Switch in the Contribution of Presynaptic and Postsynaptic NMDA Receptors to Long-Term Depression

“…Interestingly, glia have recently been shown to provide a major source of ambient and evoked glutamate (Jourdain et al, 2007;Le Meur et al, 2007). Notably, the NMDAR glycine binding sites on presynaptic NMDARs appear to be saturated, unlike postsynaptic NMDARs, suggesting that presynaptic NMDARs are primed to be activated by glutamate (Li and Han, 2007). Currently it is unknown whether presynaptic NMDARs require depolarization for their activation.…”

“…This tLTD is expressed presynaptically as a reduction in the probability of neurotransmitter release. Presynaptic NMDARs are also involved in neurotransmission in L2/3 of visual cortex (Li and Han, 2007) and tLTD induction at L2/3 in barrel cortex of young rodents (Bender et al, 2006b). Although growing evidence suggests an important role for presynaptic NMDARs early in development (Lien et al, 2006), it remains unknown whether presynaptic NMDARs are regulated in a laminar or developmental manner.…”

Presynaptic NMDA receptors: dynamics and distribution in developing axons in vitro and in vivo

“…Elegant work has provided evidence that NMDARs regulate presynaptic plasticity in the visual and somatosensory neocortex, entorhinal cortex, hippocampus, amygdala, cerebellum and spinal cord (Bardoni et al, 2004;Bender et al, 2006;Berretta and Jones, 1996;Brasier and Feldman, 2008;Buchanan et al, 2012;Casado et al, 2000;Casado et al, 2002;Corlew et al, 2007;Duguid and Smart, 2004;Fiszman et al, 2005;Glitsch and Marty, 1999;Humeau et al, 2003;Jourdain et al, 2007;Li and Han, 2007;Li et al, 2008;Liu et al, 1997;Mameli et al, 2005;Rodríguez-Moreno et al, 2011;Rodríguez-Moreno and Paulsen, 2008;Sjöström et al, 2003;Yang et al, 2006). At least in certain developing neurons, the responsible receptors are found in the presynaptic rather than in the postsynaptic neuron.…”