1997
DOI: 10.1523/jneurosci.17-05-01604.1997
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d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

Abstract: D-Serine is localized in mammalian brain to a discrete population of glial cells near NMDA receptors, suggesting that D-serine is an endogenous agonist of the receptor-associated glycine site. To explore this possibility, we have compared the immunohistochemical localizations of D-serine, glycine, and NMDA receptors in rat brain. In the telencephalon, D-serine is concentrated in protoplasmic astrocytes, which are abundant in neuropil in close vicinity to NMDA receptor 2A/B subunits. Ultrastructural examination… Show more

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Cited by 393 publications
(374 citation statements)
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“…The relevance of this report to NMDAR currents in vivo is therefore contingent upon the NMDAR GLY site being unsaturated in brain tissue. Nonsaturation of the NMDAR GLY site in vivo has been suggested previously (Bergeron et al 1998;Chen et al 2003;Martina et al 2003Martina et al , 2004Wilcox et al 1996), despite the fact that GLY and the other NMDAR coagonist D-serine are both present in some brain regions (Papouin et al 2012;Rosenberg et al 2013;Schell et al 1997). Using glutamate uncaging in acute hippocampal slices, we find that the NMDAR responses from CA1 neurons show desensitization upon glutamate uncaging that is significantly reduced by exposure to HCY.…”
Section: Discussionmentioning
confidence: 47%
See 1 more Smart Citation
“…The relevance of this report to NMDAR currents in vivo is therefore contingent upon the NMDAR GLY site being unsaturated in brain tissue. Nonsaturation of the NMDAR GLY site in vivo has been suggested previously (Bergeron et al 1998;Chen et al 2003;Martina et al 2003Martina et al , 2004Wilcox et al 1996), despite the fact that GLY and the other NMDAR coagonist D-serine are both present in some brain regions (Papouin et al 2012;Rosenberg et al 2013;Schell et al 1997). Using glutamate uncaging in acute hippocampal slices, we find that the NMDAR responses from CA1 neurons show desensitization upon glutamate uncaging that is significantly reduced by exposure to HCY.…”
Section: Discussionmentioning
confidence: 47%
“…Data-based modeling experiments have presumed that the synaptic [GLY] in GlyT expressing brain areas is below 150 nM (Attwell et al 1993;Roux and Supplisson 2000), which, by design, resembles the concentration used in our culture experiments. D-Serine, a second in vivo coagonist of the NMDAR GLY site, is strongly expressed in the forebrain (Schell et al 1997;Wolosker 2006 for review) and may be the primary NMDAR coagonist at some synapses (Papouin et al 2012). Nonetheless, adding extracellular GLY or D-serine to forebrain slice preparations, or blocking GlyT to allow accumulation of synaptic GLY, enhances evoked NMDAR currents in brain slices (Bergeron et al 1998;Chen et al 2003;Martina et al 2003), indicating that the combination of D-serine and GLY Fig.…”
Section: Hcy Effect On Nmdar Currents Depends On Glun2 Subunit Compmentioning
confidence: 99%
“…In most parts of the brain, D-serine's histochemical localizations match those of NMDA receptors much more closely than do those of glycine, consistent with a role for D-serine as the principal endogenous agonist for NMDA receptors, especially in the hippocampus where selective degradation of D-serine profoundly reduces NMDA neurotransmission (3). By contrast, in the adult cerebellum D-serine levels are very low, and localizations of glycine match those of NMDA receptors better than D-serine, suggesting that in the cerebellum glycine may be the principal endogenous agonist in the adult (29). In the neonatal cerebellum, however, D-serine levels are high, peaking at the time of granule cell migration, which suggests that the principal role of D-serine in the developing cerebellum is to serve as a coagonist for NMDA receptor-dependent granule cell migration.…”
Section: Discussionmentioning
confidence: 70%
“…[19][20][21] Glia also release D-serine in response to stimulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. 22 D-serine stimulates the glycine-B coagonist site of the NMDA receptor. Thus, glial loss could contribute to reductions in NMDA receptor function.…”
Section: Glutamatergic Abnormalities In Mood Disordersmentioning
confidence: 99%