a, Training regimen for naive, late-trained, and early-trained mice; each line represents 8 trials/day. Early training started at 4 weeks of age; late training started at 11 weeks of age. Late- and early-trained mice received the same number of training trials. b-d, Spatial memory performance in the water maze. (b) WT naive (n = 18), WT late-trained (n = 18), WT early-trained (n = 19), Rett naive (n = 19), Rett late-trained (n = 19), and Rett early-trained (n = 18) mice were tested over 4 consecutive days at 12 weeks of age. A probe trial on day 5 measured the time spent in the target quadrant (c) and number of platform area crossings (d). e, Early-trained WT (n = 7) and Rett mice (n = 7) mice were tested until 24 weeks of age and then compared to naive Rett mice (n = 12) at 12 weeks of age. In a subset of Rett mice (n = 8), training was delayed until 8 weeks of age. f-g, Conditioned fear memory in water maze-trained mice. Contextual (f) and cued memory (g) were assessed in WT naive (n = 11), WT late-trained (n = 11), WT early-trained (n = 12), Rett naive (n = 12), Rett late-trained (n = 12), and Rett early-trained (n= 11) mice. The sample size (n) corresponds to the number of biologically independent mice. Data are represented as mean ± s.e.m. Statistical significance was determined using a two-way ANOVA with Tukey’s multiple comparisons test; ns (p>0.05), ** (p<0.01), **** (p<0.0001).