Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 2, Pages E204-E213Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1416668112
Keywords
NMDA receptors; coagonist; synapse; developmental switch; hippocampus
Categories
Funding
- National Institute of Child Health and Human Development
- Direction Generale de l'Armement
- Centre National de la Recherche Scientifique
- France Alzheimer
- Universite Aix-Marseille
- Universite Paris Descartes
- Agence Nationale de la Recherche
- Fondo di Ateneo per la Ricerca
- Israel Science Foundation
- Legacy Heritage Fund
- Allen and Jewel Prince Center for Neurodegenerative Disorders of the Brain
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available