The Rise and Fall of the D-Serine-Mediated Gliotransmission Hypothesis

Herman Wolosker, Darrick T. Balu, Joseph T. Coyle

Research output: Contribution to journalReview articlepeer-review

Abstract

D-Serine modulates N-methyl D-aspartate receptors (NMDARs) and regulates synaptic plasticity, neurodevelopment, and learning and memory. However, the primary site of D-serine synthesis and release remains controversial, with some arguing that it is a gliotransmitter and others defining it as a neuronal cotransmitter. Results from several laboratories using different strategies now show that the biosynthetic enzyme of D-serine, serine racemase (SR), is expressed almost entirely by neurons, with few astrocytes appearing to contain D-serine. Cell-selective suppression of SR expression demonstrates that neuronal, rather than astrocytic D-serine, modulates synaptic plasticity. Here, we propose an alternative conceptualization whereby astrocytes affect D-serine levels by synthesizing L-serine that shuttles to neurons to fuel the neuronal synthesis of D-serine.

Original languageEnglish
Pages (from-to)712-721
Number of pages10
JournalTrends in Neurosciences
Volume39
Issue number11
DOIs
StatePublished - 1 Nov 2016

Keywords

  • D-serine
  • N-methyl D-aspartate receptor
  • gliotransmission
  • glycine
  • serine racemase
  • synaptic plasticity

All Science Journal Classification (ASJC) codes

  • General Neuroscience

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