title: D-Serine and Glycine Differentially Control Neurotransmission during Visual Cortex Critical Period.
abstract: N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity. Their activation requires the binding of both glutamate and d-serine or glycine as co-agonist. The prevalence of either co-agonist on NMDA-receptor function differs between brain regions and remains undetermined in the visual cortex (VC) at the critical period of postnatal development. Here, we therefore investigated the regulatory role that d-serine and/or glycine may exert on NMDARs function and on synaptic plasticity in the rat VC layer 5 pyramidal neurons of young rats. Using selective enzymatic depletion of d-serine or glycine, we demonstrate that d-serine and not glycine is the endogenous co-agonist of synaptic NMDARs required for the induction and expression of Long Term Potentiation (LTP) at both excitatory and inhibitory synapses. Glycine on the other hand is not involved in synaptic efficacy per se but regulates excitatory and inhibitory neurotransmission by activating strychnine-sensitive glycine receptors, then producing a shunting inhibition that controls neuronal gain and results in a depression of synaptic inputs at the somatic level after dendritic integration. In conclusion, we describe for the first time that in the VC both D-serine and glycine differentially regulate somatic depolarization through the activation of distinct synaptic and extrasynaptic receptors.
authors.affiliation: Institut de Neuroscience Paris-Saclay (NeuroPSI), UMR 9197 CNRS-Université Paris-Sud, Bât 446, F-91405, Orsay cedex, France.
authors.forename: Claire N J
authors.initials: CN
authors.lastname: Meunier
authors.affiliation: Aix-Marseille University, CRN2M UMR7286 CNRS, 51 Bd Pierre Dramard, 13344, Marseille, France.
authors.forename: Glenn
authors.initials: G
authors.lastname: Dallérac
authors.affiliation: Institut de Neuroscience Paris-Saclay (NeuroPSI), UMR 9197 CNRS-Université Paris-Sud, Bât 446, F-91405, Orsay cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Le Roux
authors.affiliation: Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, via J.H. Dunant 3, Varese, Italy.|"The Protein Factory", Centro Interuniversitario di Biotecnologie Proteiche, Politecnico di Milano, ICRM-CNR, Milano, Italy.|Università degli Studi dell'Insubria, via Mancinelli 7, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sacchi
authors.affiliation: Aix-Marseille University, CRN2M UMR7286 CNRS, 51 Bd Pierre Dramard, 13344, Marseille, France.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Levasseur
authors.affiliation: Institut de Neuroscience Paris-Saclay (NeuroPSI), UMR 9197 CNRS-Université Paris-Sud, Bât 446, F-91405, Orsay cedex, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Amar
authors.affiliation: Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, via J.H. Dunant 3, Varese, Italy.|"The Protein Factory", Centro Interuniversitario di Biotecnologie Proteiche, Politecnico di Milano, ICRM-CNR, Milano, Italy.|Università degli Studi dell'Insubria, via Mancinelli 7, Milano, Italy.
authors.forename: Loredano
authors.initials: L
authors.lastname: Pollegioni
authors.affiliation: Aix-Marseille University, CRN2M UMR7286 CNRS, 51 Bd Pierre Dramard, 13344, Marseille, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mothet
authors.affiliation: Institut de Neuroscience Paris-Saclay (NeuroPSI), UMR 9197 CNRS-Université Paris-Sud, Bât 446, F-91405, Orsay cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fossier
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D014793:Visual Cortex / Q000378:metabolism*
chemical_list: D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C027822:strychnine receptor; D018698:Glutamic Acid; D012694:Serine; D005998:Glycine