Purchase this article with an account.
E. C. Gustafson, R. F. Miller; D-Amino Acid Oxidase Keeps D-Serine Levels Below Saturation for NMDA Receptors in the Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1632.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Excitatory input to retinal ganglion cells is mediated by glutamate receptors; both AMPA and NMDA type. Interestingly, NMDA receptor (NMDAR) activation requires a second "coagonist." Previously, our lab has shown that in the salamander retina, D-serine is the functional coagonist and that in the eyecup preparation the D-serine levels do not reach saturation. D-amino acid oxidase (DAO) is an endogenous enzyme that functions to metabolize D-amino acids, including D-serine. We obtained a mutant mouse with a point mutation on the DAO gene which renders it functionally inoperative. This mutant was used to investigate the importance of DAO in controlling D-serine levels in the retina and thereby affecting NMDAR activation.
Inverted eyecups from mutant (DAO-) and wild-type (Wt) mice were placed in a perfusion chamber and viewed using IR optics. Whole-cell recordings (WCRs) from retinal ganglion cells (RGCs) were used to measure responses to a 200 µm spot of light. D-serine was added to the bathing media to determine the level of coagonist saturation. AP7 was added to determine the level of NMDAR current. Some Wt eyecups were incubated in sodium benzoate, a DAO inhibitor, to acutely mimic the DAO- mutant.
In Wt mice, light responses, measured with WCRs in both current- and voltage-clamp configurations, were increased following D-serine application. Similar recordings from the DAO- mouse did not show changes in light-evoked responses when D-serine was added to the bathing medium. The action of D-serine was dependent on NMDAR activity, since blocking NMDARs with AP7 eliminated the effects of D-serine. While both DAO- and Wt mice showed a substantial NMDAR component in their light responses, when measured in voltage clamp, the NMDAR portion of the response in DAO- mice was twice as large as that in Wt mice. Following a two hour incubation in sodium benzoate, WCRs from Wt retinas were not affected by the addition of D-serine.
This PDF is available to Subscribers Only