Fig. 5.

Precipitation of behavioral phenotype in R6/2 mice following injection of HTTExon1Q48 fibrils. Atlas coordinates for intraventricular injections, treatment legend (a) and experimental timeline (b). Clasping score in R6/2 mice at all tested time points (c) and at 4 weeks of age (d). Duration of full-clasping behavior at all tested time points (e) and at 12 weeks of age (f) WT BSA n = 13–14; WT HTTExon1Q25 n = 11–13; WT HTTExon1Q48 n = 12–15; R6/2 BSA n = 11–14; R6/2 HTTExon1Q25 n = 12–18; R6/2 HTTExon1Q48 n = 9–19. Motor endurance was measured by assessing the distance traveled in the last 5 min of the open field at 4 weeks post-injection for male (g) and female mice (h). WT BSA n = 9F, 4M; WT HTTExon1Q25 n = 3F, 10M; WT HTTExon1Q48 n = 8F, 9M; R6/2 BSA n = 7F, 9M; R6/2 HTTExon1Q25 n = 7F, 10M; R6/2 HTTExon1Q48 n = 11F, 8M. At 4 weeks post-injection, short-term memory was evaluated by assessing the change in distance traveled between the first 5 min and min 25–30 of testing (i) and at 8 weeks post-injection, long-term memory was measured by calculating the change in distance traveled between the first 10 min of testing at 4 and 8 weeks post-injection (j). WT BSA n = 12–13; WT HTTExon1Q25 n = 12–13; WT HTTExon1Q48 n = 14–15; R6/2 BSA n = 12–16 R6/2 HTTExon1Q25 n = 16–17; R6/2Q HTTExon148 n = 16–19. Anxiety-like behavior was assessed in the light–dark box using time spent in the light box at 4, 8 and 12 weeks of age (k) and at 8 weeks only (l) and latency to emerge head at 4, 8 and 12 weeks of age (m) and at 12 weeks only (n). WT HTTExon1Q25 n = 11–14; WT HTTExon1Q48 n = 11–17; R6/2 HTTExon1Q25 n = 8–14; R6/2 HTTExon1Q48 n = 8–17. Data are expressed as mean ± SEM. For c, i, k, and m, statistics were calculated using a linear mixed effects model. For all other graphs, statistics were performed using a two-way ANOVA with Tukey’s post hoc test. *p < 0.05, **p < 0.01. AP antero-posterior, CTX cortex, DV dorso-ventral, LV lateral ventricle, ML medio-lateral, STR striatum, w weeks, WT wild type, M male, F female