Spectral and Temporal Sensitivity of Cone-Mediated Responses in Mouse Retinal Ganglion Cells

Abstract

The retina uses two photoreceptor types to encode the wide range of light intensities in the natural environment. Rods mediate vision in dim light, whereas cones mediate vision in bright light. Mouse photoreceptors include only 3% cones, and the majority of these co-express two opsins (S, M), with peak sensitivity to either ultraviolet (360 nm) or green light (508 nm). The M:S opsin ratio varies across the retina but has not been characterized functionally, preventing quantitative study of cone-mediated vision. Furthermore, physiological and behavioral measurements suggested that mouse retina supports relatively slow temporal processing (peak sensitivity, ~2–5 Hz), compared to primates; however, past studies used visible wavelengths that are inefficient at stimulating mouse S opsin. Here, we measured the M:S opsin expression ratio across the mouse retina, as reflected by ganglion cell responses, in vitro, and probed cone-mediated ganglion cell temporal properties using ultraviolet light stimulation and linear systems analysis. From recordings in mice lacking rod function (Gnat1−/−, Rho−/−), we estimate ~70% M-opsin expression in far dorsal retina, dropping to <5% M-opsin expression throughout ventral retina. In mice lacking cone function (Gnat2cpfl3), light-adapted rod-mediated responses peaked at ~5–7 Hz. In wild-type mice, cone-mediated responses peaked at ~10 Hz, with substantial responsiveness up to ~30 Hz. Therefore, despite the small percentage of cones, cone-mediated responses in mouse ganglion cells are fast and robust, similar to those in primates. These measurements enable quantitative analysis of cone-mediated responses at all levels of the visual system.

G-protein–mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer

“…Fig. 1D illustrates the response of an RBC to a 10-ms full-field flash of 425 nm light delivering 3.6 photons/µm 2 , a flash strength that will activate only rods (21)(22)(23). At a concentration of 10 nM, dialysis of Gβγ resulted in a slow depression of the light response, reaching a steady-state value of 39.0 ± 6.5 of the response at break-in after 10 min of dialysis, ( (2).…”

Imaging light responses of retinal ganglion cells in the living mouse eye

“…To compare the visual impact on photoreceptors of the various imaging and stimulation lights, we calculated isomerization rates for mouse M and S pigments and rhodopsin using methods described by Naarendorp (2010) (see also, Wang et al 2011) (Fig. 1, A and B).…”

“…As shown in Fig. 1A, 365-nm light is near the peak sensitivity of mouse S cones (Jacobs and Rowe 2004;Lyubarsky et al 1999;Nikonov et al 2006) and activates both S cones and the many cones that coexpress M and S opsins (Applebury et al 2000;Haverkamp et al 2005;Jacobs and Williams 2007;Rohlich et al 1994;Wang et al 2011). To reduce the visual impact of the 488-nm imaging light on S cones, the intensity of the UV stimulus was set ϳ3 log 10 units above that of the 488-nm fluorescence imaging light (Fig.…”

“…For example, in this study the excitation wavelength was 488 nm, which is close to the peak sensitivity of mouse middle-wavelength sensitive (M) cone opsin and rhodopsin Lyubarsky et al 1999Lyubarsky et al , 2004. To separate visual activation from response to the imaging light, we used ultraviolet (UV) light (365 nm) to stimulate the retina thus selectively activating the short-wavelength sensitive (S) cone opsin, which activates most retinal ganglion cells (Wang et al 2011).…”

“…We could not directly calculate the isomerization rates produced by infrared lights used for reflectance imaging and wavefront sensing, which should be far less than that calculated for a 700-nm light of similar power (200 W at pupil; light gray bar). Horizontal line corresponds to an isomerization rate of 5,200 Rh*·photoreceptor Ϫ1 ·s Ϫ1 and was used to visualize the start of photopic vision in mouse (Naarendorp et al 2010;Wang et al 2011), where rod saturation begins.…”