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. 2016 Nov 9;36(45):11544–11558. doi: 10.1523/JNEUROSCI.1279-16.2016

Figure 4.

Figure 4.

Neuronal silencing exclusively induced by CNO in hM4Di Tg mice. A, Locomotor activity was evaluated by measuring the distance moved by WT and hM4Di Tg mice administered vehicle or CNO before assessments (n = 6 per group). There was a significant main effect of CNO administration (F(1, 20) = 7.5, p < 0.05 by two-way ANOVA), but not genotype of animals (F(1, 20) = 2.34, p > 0.05 by two-way ANOVA). However, a significant interaction between these two parameters was observed (p < 0.01 by two-way ANOVA). Post hoc analysis revealed a significant decrease in locomotor activity in CNO-treated Tg mice compared with control Tg or CNO-treated WT mice (**p < 0.01, Bonferroni), but no significant difference was observed between control and CNO-treated WT mice (p > 0.05, Bonferroni). B–E, Assessment of neuronal activity by ASL-MRI. Top and bottom demonstrate representative brain images at baseline and after administration of CNO, respectively, in WT (B) and hM4Di Tg (D) mice. Left and right represent coronal sections at −1.9 mm and −6.6 mm anterior to the bregma mainly containing the neocortex/hippocampus and cerebellum regions, respectively. Quantitative analyses of CNO-induced CBF changes in WT (n = 3) and hM4Di Tg (n = 5) mice are shown in C and E, respectively. In WT mice, there was a significant main effect of region (F(1, 24) = 22.91, p < 0.01 by two-way ANOVA) but not CNO treatment (F(1, 24) = 0.313, p > 0.05 by two-way ANOVA) on CBF measures. No interaction between these two parameters was found (p > 0.05 by two-way ANOVA) and post hoc analyses did not indicate any significant difference in CBF between baseline and CNO treatment (p > 0.05 by Bonferroni's test). In Tg mice, there were significant main effects of CNO administration (F(1, 24) = 9.70, p < 0.01 by two-way ANOVA) and region (F(2, 24) = 5.30, p < 0.05) on CBF measures. CBF was decreased significantly in the neocortex (CT) and hippocampus (Hip), but not in the cerebellum (CB), after CNO administration in hM4Di Tg mice (*p < 0.05, **p < 0.01, by Bonferroni's test for multiple comparisons after ANOVA, compared with baseline in corresponding regions), whereas CNO administration had no significant effect on CBF in any assayed regions in WT mice. Error bars indicate SE.