Respective contribution of glycine and glial D-serine to NMDA receptor activity in the hippocampus
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1
Institut Francois Magendie, INSERM U862, France
NMDA receptors (NMDARs) are unique among the synaptic receptor family in that their opening requires the binding of glutamate and of a co-agonist. The latter has long been thought to be glycine, a ubiquitous and abundant amino acid, but recent findings suggest that the gliotransmitter D-serine could also act as such a co-agonist. Here we investigated the respective contribution of glycine and D-serine in controlling NMDAR activity at hippocampal CA3-CA1 synapses, in acute rat brain slices. Application of D-amino acid oxidase (DAAO), an enzyme degrading D-serine specifically, dramatically reduced NMDAR-mediated fEPSPs while, in contrast, application of glycine oxidase (GO), an enzyme degrading glycine specifically, had no significant effect on NMDA fEPSPs. Importantly, DAAO inhibitory action was compromised in slices pre-incubated with saturating concentrations of glycine, which demonstrates the specificity of DAAO action. Furthermore, under these conditions, subsequent addition of GO markedly diminished NMDA-fEPSPs, this demonstrates GO efficacy. In addition, perfusion of fluoroacetate (FAC), a glial metabolic inhibitor, produced a reduction of NMDA fEPSPs that could be rescued by exogenous application of D-serine or blocked by saturating concentrations of glycine. Consistently, application of FAC abolished long-term potentiation (LTP) which could be restored by exogenous application of D-serine. We thus demonstrate for the first time that, at CA3-CA1 hippocampal synapses, glycine is not an endogenous ligand of the glycine-site of NMDARs. This role is ensured by D-serine, which is, at least in part, of glial origin. Our data further demonstrate that glial cells are key players in controlling important synaptic phenomenon such as LTP.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Symposium10 – Neuron-glial communications in the normal and pathological brain
Citation:
Oliet
S
(2009). Respective contribution of glycine and glial D-serine to NMDA receptor activity in the hippocampus.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.159
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Received:
26 Nov 2009;
Published Online:
26 Nov 2009.
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Correspondence:
Stephane Oliet, Institut Francois Magendie, INSERM U862, Bordeaux, France, stephane.oliet@inserm.fr