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E. C. Gustafson, E. R. Stevens, R. F. Miller; NMDA Receptor Coagonist Occupancy is Altered by Light Stimulus Contrast. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1862.
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NMDA receptors require the simultaneous binding of both glutamate and a coagonist (either D-serine or glycine). Previous studies showed that the coagonist sites of retinal NMDARs are not fully occupied, suggesting the possibility of modulation of neuronal excitability through the availability/release of coagonist. Here we investigated whether changes in stimulus size or intensity would affect coagonist availability and NMDAR activity.
Two electrophysiological techniques were used in this study to measure inner retina light responses in the tiger salamander. Whole-cell recordings were used to study the light responses of retinal ganglion cells under a series of stimulus diameters and contrast levels. The Proximal Negative Field Potential (PNFP) was used to record extracellular responses from the proximal retina over a series of light intensities. The occupancy state of the NMDAR coagonist site was determined by repeating the stimulus series in the presence of D-serine. The level of NMDAR activity under the stimulus conditions was also studied using NMDAR blockers.
In recordings from retinal ganglion cells, no difference was seen in the percent enhancement of currents in the presence of D-serine or in the percent of the response mediated by NMDAR currents when the diameter of the stimulus was varied from 50-1200 µm. In contrast, the level of D-serine potentiation declined and NMDAR contributions grew as the contrast levels of a fixed diameter stimulus (250 µm) were increased (± 1.0 log units). Extracellular recordings of the PNFP, preformed over a larger range of contrasts (7 log units), demonstrated a large D-serine enhancement at low contrasts, a precipitous decline as the contrast was increased, and no augmentation at the highest levels of contrast.
The results from this study demonstrate that the availability of NMDAR coagonist in the inner retina is determined, in part, by the nature of the stimulus. Stimuli of larger contrasts resulted in saturation of the NMDAR coagonist site, suggesting that coagonist is released in a stimulus-dependent manner and that the level of NMDAR activation is controlled by its availability.
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