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Robert F. Miller, Steven J. Sullivan, Eric C. Gustafson, Catherine W. Morgans, Manuel Esguerra; D-serine Determines The AMPA/NMDA Receptor Ratios In Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1945.
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© ARVO (1962-2015); The Authors (2016-present)
We explored the role of D-serine as one factor in determining the relative population of light-activated NMDA and AMPA receptors in ganglion cells of the mouse retina.
Whole-cell recordings from ganglion cells were obtained using an isolated, perfused retina preparation. Two strains of mice were studied that provided either an excess of D-serine (D-amino acid oxidase (DAO) deficient) or reduced D-serine levels (serine racemase knockout (SR-KO)) when compared to their wildtype controls. In addition, Western blots and immunostaining procedures were carried out using antibodies that label NMDA and AMPA receptor subtypes. D-serine levels were measured using capillary electrophoresis (CE) separation and detection techniques.
When D-serine levels are higher than normal (DAO-deficient), light-evoked ganglion cell responses are dominated by NMDA receptors. In contrast, when D-serine levels are reduced (SR-KO), light-evoked responses of retinal ganglion cells are driven almost entirely by AMPA receptors. Western blots and immunostaining revealed differences in relative levels of AMPA and NMDA receptors, depending on the genotype of the mice.
Retina levels of D-serine play a role in determining the NMDA to AMPA receptor ratio within the ganglion cell population of the mouse retina. It appears that during the course of development, D-serine plays an important regulatory role in shaping the functional expression of NMDA and AMPA receptors of retinal ganglion cells.
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