Fig. 6: LL-341070 treatment accelerates recovery of visual function after demyelination.

A As a terminal procedure, three Neuropixel probes inserted in V1 record neuronal activity during visual stimuli presentation. B Experimental timeline. C Representative traces (with SEM) of single-neuron responses to dark flash. Dashed line at stimulus onset. D Demyelination delays single neuron responses to flash (dark and bright). E High dose LL-341070 restores single neuron latencies to flash (dark and bright) by 3 weeks. F Representative VEPs in response to a dark flash. Dashed line at stimulus onset. G, H VEP N70 latency to flash (dark and bright) is not significantly altered by demyelination (G) or treatment at 3 weeks (H). I Demyelination distorts VEP shape in response to flash (dark and bright). J High dose LL-341070 rescues VEP shape distortion by 3 weeks. In (D), Wilcoxon (Z = 4.37, ***p < 0.0001). Healthy: n = 104 responses from 6 probes from 3 mice, demyelinated: n = 55 responses from 7 probes from 5 mice. In (E), Kruskal-Wallis (F(3) = 43.17, ***p < 0.0001). Steel-Dwass (vehicle vs. healthy: ***p < 0.0001; 0.1 mg/kg vs. healthy: ***p < 0.0001; 0.3 mg/kg vs. 0.1 mg/kg: ***p = 0.0002; 0.3 mg/kg vs. vehicle *** p = 0.0022). Vehicle: n = 157 responses from 8 probes from 3 mice, 0.1 mg/kg: n = 40 responses from 6 probes from 4 mice, 0.3 mg/kg: n = 76 responses from 4 probes from 2 mice, healthy: n = 104 responses from 6 probes from 3 mice. In (G), Wilcoxon (Z = −0.79, p = 0.43). Healthy: n = 6 VEPs from 3 probes from 2 mice, demyelinated: n = 20 VEPs from 10 probes from 4 mice. In (H), Kruskal-Wallis (F(3) = 6.11, p = 0.11). Vehicle: n = 18 VEPs from 9 probes from 3 mice, 0.1 mg/kg: n = 11 VEPs from 8 probes from 3 mice, 0.3 mg/kg: n = 12 VEPs from 6 probes from 2 mice, healthy: n = 6 VEPs from 3 probes from 2 mice. In (I), Wilcoxon (Z = −3.13, **p = 0.0017). Healthy: n = 6 VEPs from 3 probes from 2 mice, demyelinated: n = 20 VEPs from 10 probes from 4 mice. In (J), Kruskal-Wallis (F(3) = 20.38, ***p = 0.0001). Steel-Dwass (vehicle vs. healthy: *p = 0.024, 0.1 mg/kg vs. healthy: **p = 0.006, 0.3 mg/kg vs. 0.1 mg/kg ***p = 0.0005). Vehicle: n = 18 VEPs from 9 probes from 3 mice, 0.1 mg/kg: n = 11 VEPs from 8 probes from 3 mice, 0.3 mg/kg: n = 12 VEPs from 6 probes from 2 mice, healthy: n = 6 VEPs from 3 probes from 2 mice. *p < 0.05, **p < 0.01, ***p < 0.001; median, IQR (box), min./max. (whiskers) in (D, E, G, H, I, J); data points color-coded by mouse in (D, E, G, H, I, J); two-sided statistical tests. See Supplementary Data 1 for statistical details and Source Data file for source data. VEP=visual evoked potential.