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Manuel Esguerra, Amy Silberschmidt, Robert Miller; Role of the NMDA receptor coagonist D-serine in retinal function measured with the optokinetic reflex. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3404. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
This study expands our ongoing analysis of NMDA receptor modulation in synaptic function of the retina to the behavioral realm. Our previous studies have shown that D-serine availability is critical to generation of light-evoked synaptic responses in ganglion cells of isolated mouse retinas. In the current study, we used eye movements generated by the optokinetic reflex to determine how modulating NMDA receptor function through genetic alterations in retinal D-serine levels alters contrast and temporal sensitivity in the retinas of intact animals.
Conscious mice with surgically implanted headposts were restrained inside a cylindrical drum. A computer-generated, rotating vertical grating was projected onto the inside of the drum, filling the animal's visual field. With the mouse's head held stationary, such stimuli elicit a powerful optokinetic response, in which the eye follows the drift of the stimulus to stabilize the image on the retina (Cahill and Nathans 2008). The mouse's eye movements were visualized with an infrared camera and captured with eye-tracking software (ISCAN). A unit eye tracking movement (ETM) was defined as a period of horizontal smooth pursuit, followed by a saccade to reset the eye position. The data were converted into two parameters: number of ETMs per unit time, and the ETM gain (angular velocity of the eye relative to angular velocity of the moving stimulus). Systematic alterations in grating contrast, spatial frequency, and temporal frequency were used to determine thresholds and to generate sensitivity curves.
This technique elicited robust, easily quantified eye tracking movements in both wild-type and D-serine mutant mice. A complete contrast or spatial frequency series could be collected to threshold in 20 minutes or less, and differentiation of ETM traces allowed simple, nearly automated detection of eye movements.
The OKR allows recording of reliable contrast sensitivity and spatial frequency tuning curves for both wild-type and D-serine mutant mice. Our observations indicate that altered levels of D-serine in the mouse retina modulate parameters of the optokinetic response.
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