ArticleProceedings of the National Academy of Sciences of the United States of America2015
Identity of the NMDA receptor coagonist is synapse specific and developmentally regulated in the hippocampus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 141 citations in OpenAlex.
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- Perisynaptic Astroglial Response to In Vivo Long-Term Potentiation and Concurrent Long-Term Depression in the Hippocampal Dentate Gyrus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Impact of D-Amino Acids in Schizophrenia.Biomolecules · 2025Review
- Differential Astrocyte-Supplied NMDAR Co-Agonist for CA1 Versus Dentate Gyrus Long-Term Potentiation.Hippocampus · 2025Article
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- Early involvement of D-serine in β-amyloid-dependent pathophysiology.Cellular and molecular life sciences : CMLS · 2025Article
- An increased copy number of glycine decarboxylase (GLDC) associated with psychosis reduces extracellular glycine and impairs NMDA receptor function.Molecular psychiatry · 2025Article
- SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- DTD1 modulates synaptic efficacy by maintaining D-serine and D-aspartate homeostasis.Science China. Life sciences · 2025Article
- A new type of blood-brain barrier aminoacidopathy underlies metabolic microcephaly associated with SLC1A4 mutations.Brain : a journal of neurology · 2024Article
- d-Serine Inhibits Non-ionotropic NMDA Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- L-serine deficiency: on the properties of the Asn133Ser variant of human phosphoserine phosphatase.Scientific reports · 2024Article
- Cross species review of the physiological role of D-serine in translationally relevant behaviors.Amino acids · 2023Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.