ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Postsynaptic Serine Racemase Regulates NMDA Receptor Function.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026Review
- Cognitive loss after brain trauma results from sex-specific activation of synaptic pruning processes.Brain : a journal of neurology · 2026Article
- mtDNA leakage promotes neuron-glia crosstalk to induce epilepsy by cGAS-STING-driven neuroinflammation and serine metabolic reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Microglial serine racemase knockout alleviates Alzheimer-like neuropathology and behavioral deficit via lactylation-mediated anti-inflammation.Communications biology · 2026Article
- D-Serine's Journey Between Stars and Synapses.Neurochemical research · 2025Review
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- D-Serine May Ameliorate Hippocampal Synaptic Plasticity Impairment Induced by Patients' Anti-N-methyl-D-aspartate Receptor Antibodies in Mice.Biomedicines · 2024Article
- Targeted Chiral Metabolomics of D-Amino Acids: Their Emerging Role as Potential Biomarkers in Neurological Diseases with a Focus on Their Liquid Chromatography-Mass Spectrometry Analysis upon Chiral Derivatization.International journal of molecular sciences · 2024Review
- Comparative Genomics of the World's Smallest Mammals Reveals Links to Echolocation, Metabolism, and Body Size Plasticity.Genome biology and evolution · 2024Article
- Article
- D-Cycloserine enhances the bidirectional range of NMDAR-dependent hippocampal synaptic plasticity.Translational psychiatry · 2024Article
- Serine racemase deletion alters adolescent social behavior and whole-brain cFos activation.Frontiers in psychiatry · 2024Article
- Cross species review of the physiological role of D-serine in translationally relevant behaviors.Amino acids · 2023Review
- KCTD13-mediated ubiquitination and degradation of GluN1 regulates excitatory synaptic transmission and seizure susceptibility.Cell death and differentiation · 2023Article
- D-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation.Scientific reports · 2023Article
- ASC Transporters Mediate D-Serine Transport into Astrocytes Adjacent to Synapses in the Mouse Brain.Biomolecules · 2023Article
- Detection and analysis of chiral molecules as disease biomarkers.Nature reviews. Chemistry · 2023Review
- Article
- Natural variation in gene expression and viral susceptibility revealed by neural progenitor cell villages.Cell stem cell · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
d-serine is the primary NMDAR coagonist at mature forebrain synapses and is synthesized by the enzyme serine racemase (SR). However, our understanding of the mechanisms regulating the availability of synaptic d-serine remains limited. Though early studies suggested d-serine is synthesized and released from astrocytes, more recent studies have demonstrated a predominantly neuronal localization of SR. More specifically, recent work intriguingly suggests that SR may be found at the postsynaptic density, yet the functional implications of postsynaptic SR on synaptic transmission are not yet known. Here, we show an age-dependent dendritic and postsynaptic localization of SR and d-serine by immunohistochemistry and electron microscopy in mouse CA1 pyramidal neurons. In addition, using a single-neuron genetic approach in SR conditional KO mice from both sexes, we demonstrate a cell-autonomous role for SR in regulating synaptic NMDAR function at Schaffer collateral (CA3)-CA1 synapses. Importantly, single-neuron genetic deletion of SR resulted in the elimination of LTP at 1 month of age, which could be rescued by exogenous d-serine. Interestingly, there was a restoration of LTP by 2 months of age that was associated with an upregulation of synaptic GluN2B. Our findings support a cell-autonomous role for postsynaptic neuronal SR in regulating synaptic NMDAR function and suggests a possible autocrine mode of d-serine action.
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Registered trials
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.