NMDA receptors, glycine and D-serine : a subtle “menage a trois”
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1
Neurocentre Magendie, INSERM U862, France
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2
Universite de Bordeaux, France
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3
Ecole Normale Superieure, Faculty of Electrical Engineering and Computing, France
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4
University of Insubria , Department of Biotechnology and Molecular Sciences, Italy
NMDA receptors (NMDARs) are key players of synaptic transmission and plasticity, which are localized at synaptic but also extrasynaptic sites. Their activation requires the binding of glutamate and of a second (co)-agonist, glycine and/or D-serine. However, the respective contribution of these two amino acids in controlling NMDAR activity is unclear and whether this contribution depends on receptor location is unknown. We address these issues in CA1 pyramidal neurons in acute rat brain slices. We obtained recordings of NMDAR-mediated field excitatory post-synaptic potentials (fEPSPs) elicited at CA3-CA1 synapses in response to the stimulation of Schaffer collaterals. Using D-amino acid oxidase (DAAO) and glycine oxidase (GO), two enzymes specifically degrading D-serine and glycine respectively, we demonstrated that NMDAR activity was not affected by reducing glycine levels whereas it was significantly impaired in the presence of the D-serine scavenger. These data confirm that D-serine is an endogenous ligand of NMDARs in this structure and rule out a role for glycine at these synapses. Furthermore, we showed that D-serine originates at least in part from glial cell as revealed by the use of the glial metabolic blocker fluoroacetate. Extrasynaptic NMDARs activity was assessed on CA1 pyramidal neurons voltage-clamped at +40 mV, through NMDA puff-evoked responses or directly by monitoring extrasynaptic NMDARs-mediated tonic current. Unlike synpatic NMDAR-mediated activity, we found that GO selectively affected responses mediated by extrasynaptic NMDARs. Thus, we demonstrate that glycine, while playing no role at synaptic location, is an endogenous co-agonist of extrasynaptic NMDARs.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Citation:
Papouin
T,
Sacchi
S,
Pollegioni
L,
Mothet
JP and
Oliet
SH
(2009). NMDA receptors, glycine and D-serine : a subtle “menage a trois”.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.175
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Received:
26 Nov 2009;
Published Online:
26 Nov 2009.
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Correspondence:
Thomas Papouin, Neurocentre Magendie, INSERM U862, Bordeaux, France, thomas.papouin@inserm.fr