Electrophysiological Analysis of the Modulation of NMDA-Receptors Function by d-Serine and Glycine in the Central Nervous System
The NMDA subtypes of glutamatergic receptors (NMDARs) are unusual in that their activation requires the binding of both glutamate and a co-agonist glycine or d-serine. Whereas glycine was first suggested to play such a role, it was later established that d-serine could serve as an endogenous co-agonist at different central synapses. We still do not know the exact nature of the endogenous co-agonist(s) of NMDARs and the function of the so-called glycine B site in many brain structures. We introduced few years ago the use of enzymes that specifically degrade either d-serine or glycine to decipher the influence of these amino acids on NMDA receptors function. The use of these enzymatic scavengers represents an invaluable technique for neurophysiologists investigating the neuromodulation of the glycine B site in the CNS. Here, we describe the proper way to manipulate these enzymes during electrophysiological recordings in acute brain slices and highlight the experimental tricks.
Key wordsd-Serine Glycine NMDA receptors Co-agonist Synapse Neurons Astrocytes Recombinant oxidases Long term potentiation Glutamate
This work was supported by ANR grant (ANR-09-MNPS-022-01) and SERVIER grant to JPM. The authors are grateful to their collaborators for their support and notably to Dr Silvia Sacchi and Prof. Loredano Pollegioni for graciously providing us with the enzymes.
- 13.Turpin F R, Potier B, Dulong J R et al. (2011) Reduced serine racemase expression contributes to age-related deficits in hippocampal cognitive function. Neurobiol Aging 32, 1495–1504.Google Scholar
- 15.Job V, Marcone G L, Pilone M S, Pollegioni L (2002) Glycine oxidase from Bacillus subtilis. Characterization of a new flavoprotein. J Biol Chem 277, 6985–6993.Google Scholar
- 16.Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, Compact 3rd Edition CD-Room. Academic Press, San Diego.Google Scholar