Fig. 6: APOE4 sedentary mice have smaller neuronal calcium responses and impaired neurovascular coupling.

a Example of neuronal calcium recording obtained with two-photon microscopy (left, from E3NOEX mouse) and how ROI masks are created over neuronal soma using Suite2P (right). b Extracted traces for 3 cells show an increase in signal during presentation of the stimulus. The trace is cut into 30 s trials that have a 5-second baseline, 5-second visual stimulus and 20-second inter stimulus interval. c, d Average ΔF/F during visual stimulus shows that APOE4 sedentary mice have smaller neuronal responses to visual stimuli. Dots correspond to average ΔF/F per mouse. (3–8 mice). e NVCi is significantly reduced by APOE4 genotype and increased by exercise and exercise duration (LMM for genotype*exercise*vessel type*duration; animal ID as a random factor; genotype: p = 0.01; exercise: p = 0.004). APOE4 mice have lower NVCi over time (genotype * duration: p = 0.0005). Exercise improved NVCi in pial APOE4 vessels but not in APOE4 capillaries, which by the later timepoint were dysfunctional even in active mice (genotype*exercise*vessel type; p = 0.008; genotype*duration*vessel type; p = 0.003; genotype * exercise * duration * vessel type: p = 0.02) (30–95 pial vessels from 5–19 mice; 6–20 intermediate vessels from 3–6 mice; 11–37 capillaries from 3–7 mice). f RBCV NVCi reduces over time (LMM for genotype*exercise*vessel type*duration; animal ID as a random factor; duration: p = 0.0065) (11–47 capillaries from 3–15 mice). Individual dots correspond to each vessel. Bars and error bars: mean +/- SEM. For details on N of mice and statistical outputs see Supplementary Table 6 in Supplementary Data.