The improved passive and active avoidance in the Pde6b ^rd10 mice treated with PE ^SpRY system and gPde6b. (A–F) Pde6b ^{T to C} mice exhibit significant improvement of passive avoidance in the light–dark transition test. With the luminance increasing from 300 to 900 lux, the Pde6b^{T to C} mice demonstrate an apparent preference for staying in the dark chamber based on their behavioral parameters including time (A), distance traveled (B), rearing time (C), duration (D), velocity (E) in dark, as well as transition (F) between the chambers. (G and H) The representative traveling trajectories (G) and heat map recordings for time spent in distinct regions of the light–dark box (H) with 900 lux luminance. (I) Schematic of the shuttle box learning test. (J–Q)Pde6b^{T to C} mice demonstrate improved active avoidance both in the 5-d training session (J, L, N, and P) and following test (K, M, O, and Q); the percentage of active avoidance (J and K) and passive avoidance (L and M), latency for the first active avoidance (N and O), as well as time spent (P and Q) in the test were recorded. The mice were 120 d old at d1 of the training session, and 132 and 139 d old (that is, 118 and 125 d after treatment) at d12 and d19 of the test session, respectively. Representative data are presented as mean ± SEM; n ≥ 8 independent biological replicates. Two-way ANOVA tests with Tukey’s multiple comparisons. *, P < 0.05; **, P < 0.01; ***, P < 0.001. All of Pde6b^rd10 control mice were treated with PE^SpRY and gScrambled. All experiments were independently performed at least three times to ensure repeatable results.