Extended Data Fig. 5 |. Viral delivery of DREADD-containing AAVs labels task-specific neurons, including MeCP2⁺ and MeCP2⁻ neurons in Rett mice.

a, P0 AAV delivery of Cre-dependent mCherry into cFos^CreER mice that also contain a Cre-dependent GFP in the Rosa26 locus. Expression of mCherry in GFP⁺ neurons demonstrates that the AAVs are reactivated in task-specific neurons. b-c, Overlap between injected AAV (mCherry) and endogenous reporter (GFP) in early-trained mice at 13 weeks of age. Quantification of GFP+ cells, mCherry+ cells, and overlap in the cortex and hippocampus of WT (n = 3) and Rett (n = 4) mice (c). Scale bar, 200 μm. d-i, FosTRAP labeling in MeCP2⁺ and MeCP2⁻ neurons from AAV-injected mice trained in the Morris water maze. FosTRAP labels MeCP2⁺ neurons in the cortex (d) and hippocampus (g) of WT mice. FosTRAP labels MeCP2⁺ and MeCP2⁻ neurons in the cortex (e) and hippocampus (h) of Rett mice. Quantification in the cortex (f) and hippocampus (i) of WT (n = 3) and Rett (n = 4) mice. (*) denotes a MeCP2⁺ neuron. (#) denotes a MeCP2⁻ neuron. Scale bar, 20 μm. The sample size (n) corresponds to the number of biologically independent mice. 3–4 sections were analyzed per mouse. 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).