AMPA receptor mediated d-serine release from retinal glial cells

Steve J. Sullivan, Robert F Miller

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The N-methyl-d-aspartate receptor (NMDAR) co-agonist d-serine is important in a number of different processes in the CNS, ranging from synaptic plasticity to disease states, including schizophrenia. d-serine appears to be the major co-agonist acting on retinal ganglion cell NMDA receptors, but the cell type from which it originates and whether its release can be modulated by activity are unknown. In this study, we utilized a mutant mouse line with elevated d-serine to investigate this question. Direct measurements of extracellular d-serine using capillary electrophoresis demonstrate that d-serine can be released from the intact mouse retina through an α-amino-3-hydroxyl-5- methyl-4-isoxazole-propionate receptor (AMPAR) dependent mechanism. α-Amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-evoked d-serine release persisted in the presence of a cocktail of neural inhibitors but was abolished after administration of a glial toxin. These findings provide the first evidence that extracellular d-serine levels in the retina can be modulated, and that such modulation is contingent upon glial cell activity.

Original languageEnglish (US)
Pages (from-to)1681-1689
Number of pages9
JournalJournal of Neurochemistry
Issue number6
StatePublished - Dec 2010


  • AMPA receptor
  • NMDA receptor
  • capillary electrophoresis
  • d -serine
  • glia
  • retina

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