Fig. 1. Nf1-mutant OPCs lack adaptive proliferative responses to increased neuronal activity.

a, Mouse strains used. b, Experimental design. Tamoxifen (TAM) was given for 4 consecutive days starting at 3 weeks of age. AAV injection and cannula implantation into the premotor (M2) occurred at 4 weeks of age. Blue light stimulation at 7 weeks of age. c, Optogenetic stimulation of the ipsilateral side. Inset, the cingulum (gray), where M2 axons (blue) are concentrated. d, Representative IF images of the cingulum revealed cells expressing ChR2-eYFP (white), EdU (green) and PDGFRα (magenta). Arrows, proliferating OPCs (EdU⁺/PDGFRα⁺). Scale bar, 100 µm. e, Immunohistochemistry revealed an increased density of proliferating OPCs (EdU⁺/PDGFRα⁺) in the ipsilateral stimulated (ipsi, dark color) side, relative to the contralateral unstimulated (con, light color) side, in the brains of Nf1^WT mice (N = 12). No change between ipsilateral and contralateral sides was observed in Nf1^OPC-iHet (N = 4) and Nf1^OPC-iKO (N = 5) mice. ***P = 0.0008; *P = 0.041 (Nf1^WT contralateral versus Nf1^OPC-iKO contralateral), 0.0284 (Nf1^OPC-iHet contralateral versus Nf1^OPC-iKO contralateral). The density of new OPCs is normalized to contralateral Nf1^WT values in each cohort. Each point represents one mouse. Brown–Forsythe ANOVA test (F = 19.1) with Dunnett’s T3 multiple comparisons. Data shown as mean ± s.e.m.; two-sided; NS, not significant (P > 0.05).

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