December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
The role of D-serine in Modulating the Sensitivity of NMDA Receptors in the Vertebrate Retina
Author Affiliations & Notes
  • RF Miller
    Neuroscience
    University of Minnesota Minneapolis MN
  • KR Zahs
    Physiology
    University of Minnesota Minneapolis MN
  • EA Newman
    Neuroscience
    University of Minnesota Minneapolis MN
  • ER Stevens
    Neuroscience
    University of Minnesota Minneapolis MN
  • MH Fagerson
    Neuroscience
    University of Minnesota Minneapolis MN
  • P Kim
    Neuroscience Johns Hopkins University Baltimore MD
  • SH Snyder
    Neuroscience Johns Hopkins University Baltimore MD
  • Footnotes
    Commercial Relationships   R.F. Miller, None; K.R. Zahs, None; E.A. Newman, None; E.R. Stevens, None; M.H. Fagerson, None; P. Kim, None; S.H. Snyder, None. Grant Identification: EY03014
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 893. doi:
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    • Get Citation

      RF Miller, KR Zahs, EA Newman, ER Stevens, MH Fagerson, P Kim, SH Snyder; The role of D-serine in Modulating the Sensitivity of NMDA Receptors in the Vertebrate Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):893.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Determine the presence and function of D-serine in the vertebrate retina Methods: Immunohistochemical studies were carried out in the retinas of mice, rats and salamanders using antibodies that recognize D-serine and the D-serine synthesizing enzyme serine racemase. Parallel electrophysiological experiments were carried out using isolated, perfused retinas and retina-eyecup preparations of salamanders and rats. Results: D-serine and serine racemase are abundantly present in the inner retina of salamanders, mice and rats and can be localized predominately to Muller cells and astrocytes. The distribution of these two markers is similar and overlaps the pattern of NMDA receptor distribution. Whole-cell recordings from ganglion cells in rat and tiger salamander retinas show that responses mediated by exogenous NMDA, in a Mg-free bathing solution, are enhanced by co-application of D-serine and this enhancement is blocked by the NMDA receptor antagonist D-AP7; in addition, the NMDA response is diminished when D-amino acid oxidase is co-applied with NMDA, suggesting that enzymatic degradation of D-serine reduces its ability to enhance NMDA-mediated currents. Extracellular recordings from a postbipolar response of the inner retina (PNR) were used for further evaluating the actions of D-serine. Under conditions in which NMDA receptor contributions to the PNR are enhanced (picrotoxin, strychnine, Mg-free Ringer), the PNR is reduced by D-AP7; under these same conditions, adding D-serine to the mix results in further enhancement of the PNR and this additional enhancement is reduced by D-AP7. The PNR augmentation associated with D-serine is reduced when D-amino acid oxidase is added to the bathing medium. Furthermore, D-amino acid oxidase often reduces the endogenous NMDA receptor contribution to the PNR (in the absence of D-serine) suggesting that endogenous D-serine may contribute to NMDA receptor sensitivity. Conclusion: The findings of this study provide compelling evidence that D-serine is present in the glial cells of the vertebrate retina and may play a role in modulating NMDA receptor sensitivity. It is generally accepted that D-serine modulates NMDA receptors through interactions with the glycine binding site. The results of this study strongly suggest that this binding site is not normally saturated under the conditions of our experiments.

Keywords: 594 synapse • 415 ganglion cells • 401 excitatory amino acid receptors 
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