title: Identity of the NMDA receptor coagonist is synapse specific and developmentally regulated in the hippocampus.
abstract: NMDA receptors (NMDARs) require the coagonists D-serine or glycine for their activation, but whether the identity of the coagonist could be synapse specific and developmentally regulated remains elusive. We therefore investigated the contribution of D-serine and glycine by recording NMDAR-mediated responses at hippocampal Schaffer collaterals (SC)-CA1 and medial perforant path-dentate gyrus (mPP-DG) synapses in juvenile and adult rats. Selective depletion of endogenous coagonists with enzymatic scavengers as well as pharmacological inhibition of endogenous D-amino acid oxidase activity revealed that D-serine is the preferred coagonist at SC-CA1 mature synapses, whereas, unexpectedly, glycine is mainly involved at mPP-DG synapses. Nevertheless, both coagonist functions are driven by the levels of synaptic activity as inferred by recording long-term potentiation generated at both connections. This regional compartmentalization in the coagonist identity is associated to different GluN1/GluN2A to GluN1/GluN2B subunit composition of synaptic NMDARs. During postnatal development, the replacement of GluN2B- by GluN2A-containing NMDARs at SC-CA1 synapses parallels a change in the identity of the coagonist from glycine to D-serine. In contrast, NMDARs subunit composition at mPP-DG synapses is not altered and glycine remains the main coagonist throughout postnatal development. Altogether, our observations disclose an unprecedented relationship in the identity of the coagonist not only with the GluN2 subunit composition at synaptic NMDARs but also with astrocyte activity in the developing and mature hippocampus that reconciles the complementary functions of D-serine And Glycine In Modulating Nmdars During The Maturation Of Tripartite Glutamatergic Synapses.
authors.affiliation: Aix Marseille University, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseiille UMR7286 CNRS, F-13344 Marseille, France;
authors.forename: Matildé
authors.initials: M
authors.lastname: Le Bail
authors.affiliation: Department of Cellular Biophysics, Institute for Medical Physics and Biophysics, University of Muenster, 48149 Muenster, Germany;
authors.forename: Magalie
authors.initials: M
authors.lastname: Martineau
authors.affiliation: Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria and The Protein Factory, Politecnico di Milano, Istituto di Chimica del Riconoscimento Molecolare Consiglio Nazionale delle Ricerche Milano, and Università degli Studi dell'Insubria, 21100 Varese, Italy;
authors.forename: Silvia
authors.initials: S
authors.lastname: Sacchi
authors.affiliation: Aix Marseille University, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseiille UMR7286 CNRS, F-13344 Marseille, France;
authors.forename: Natalia
authors.initials: N
authors.lastname: Yatsenko
authors.affiliation: Department of Biochemistry, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel; and.
authors.forename: Inna
authors.initials: I
authors.lastname: Radzishevsky
authors.affiliation: Aix Marseille University, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseiille UMR7286 CNRS, F-13344 Marseille, France;
authors.forename: Sandrine
authors.initials: S
authors.lastname: Conrod
authors.affiliation: Aix Marseille University, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseiille UMR7286 CNRS, F-13344 Marseille, France;
authors.forename: Karima
authors.initials: K
authors.lastname: Ait Ouares
authors.affiliation: Department of Biochemistry, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel; and.
authors.forename: Herman
authors.initials: H
authors.lastname: Wolosker
authors.affiliation: Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria and The Protein Factory, Politecnico di Milano, Istituto di Chimica del Riconoscimento Molecolare Consiglio Nazionale delle Ricerche Milano, and Università degli Studi dell'Insubria, 21100 Varese, Italy;
authors.forename: Loredano
authors.initials: L
authors.lastname: Pollegioni
authors.affiliation: Center of Psychiatry and Neuroscience, University Paris Descartes, Sorbonne Paris City, UMR 894, 75014 Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Billard
authors.affiliation: Aix Marseille University, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseiille UMR7286 CNRS, F-13344 Marseille, France; jean-pierre.mothet@univ-amu.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mothet
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000254:growth & development / Q000378:metabolism; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D017774:Long-Term Potentiation; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D005998:Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C121001:NR2B NMDA receptor
keywords: NMDA receptors; coagonist; developmental switch; hippocampus; synapse