Figure 2.
Functional CatCh Responses in the Retina and Cortex of rd1 Mice
(A and B) Percentages of cells with spontaneous activity showing a light response at 480 nm under either 1014 photons/cm2/s (A) or 1017 photons/cm2/s (B) in retinas expressing CatCh under control of CMV (black) or SNCG (gray) at 5 × 107, 5 × 108, and 5 × 109 vg per eye (n = 4). (C) Response amplitude (normalized to the response obtained at maximum luminance) as a function of light intensity in retinas expressing CatCh under control of CMV promoter at 5 × 109 viral particle dose (n = 4, 155 cells). (D) Response amplitude (normalized to the response obtained at maximum luminance) as a function of light intensity in retinas expressing CatCh under control of the SNCG promoter at a dose of 5 × 107 (light gray; n = 4 retinas, 158 cells), 5 × 108 (dark gray; n = 4 retinas, 221 cells), and 5 × 109 (black, n = 4 retinas, 261 cells) viral particles (vg) per eye. (E) Raster plots and peri-stimulus time histogram (PSTH) showing the light response or increase in spike frequency during full-field flashes at 480 nm in a retina expressing CatCh under control of the SNCG promoter. Note that with the SNCG promoter, the curve reaches a plateau at the maximum AAV vector dose. (F–H) PSTHs (top) and corresponding raster plots (bottom) of visual cortex neurons of rd1 mice expressing SNCG-CatCh in response to 475-nm full-field flashes at three different increasing light intensities of 1015 (F), 1016 (G), and 1017 (H) photons/cm2/s, respectively. (I) Comparison of visually evoked potentials (VEPs) recorded in rd1 retinas treated with the 5 × 109 vg dose of SNCG-CatCh, compared to untreated rd1 retinas and wild-type mouse retinas. (J) Normalized cortical activity (spikes and VEP) as a function of light intensities at 475 nm (n = 3 mice). Error bars represent SEM. ***p < 0.001, statistically significant.