Extended Data Fig. 9 |. Morphological and electrophysiological benefits are evident in task-specific neurons after presymptomatic training.

a, P0 AAV delivery of YFP to assess the morphology of neurons that are not task-specific (tdT-). b-e, Morphological analysis of MeCP2⁻ hippocampal CA1 neurons that are task-specific (tdT+) and not task-specific (tdT-/YFP+) in trained Rett mice at 13 weeks of age. Sholl analysis (b), spine density (c), soma area (d), and nuclear area (e) were measured in MeCP2⁻ neurons of late-trained (n = 5) and early-trained (n = 5) Rett mice. f-j, Electrophysiological recordings of MeCP2⁻ CA1 neurons in late- and early-trained Rett mice at 13 weeks of age. f, Representative image of neurons that are task-specific (magenta) and not task-specific (no magenta), both of which were injected with biocytin (green) during recording and immunostained to determine the MeCP2 status (yellow). Frequency (g) and amplitude (h) of sIPSCs and frequency (i) and amplitude (j) of sEPSCs were measured in MeCP2⁻ neurons from late-trained (n = 10) and early-trained (n = 10) Rett mice. The sample size (n) corresponds to the number of biologically independent mice. For b-c, 10–15 neurons were analyzed per mouse. For d-e, 50–100 neurons were analyzed per mouse. For g-j, 1–3 neurons were analyzed per mouse. Data are represented as mean ± s.e.m. Statistical significance was determined using a one-way (b) or two-way (c-e, g-j) ANOVA with Tukey’s multiple comparisons test; ns (p>0.05), ** (p<0.01), **** (p<0.0001).