Figure 8. Effect of optogenetic activation of the cortico-subthalamic pathway on locomotor activities in Thy1::ChR2 mice.

To avoid a fixed-frequency effect, the STN was illuminated at frequencies between 8 and 20 Hz in a pseudorandomized order. (A) ChR2-EYFP fluorescent expression. Note that the layer V pyramidal neurons and the projecting axons both expressed ChR2. The cortical afferents into the STN also expressed ChR2. (B) Location of fiberoptic cannula. (C) Representative traces of 30-second free movements before, during, and after illumination in a mouse. Locomotor activity was significantly suppressed by cortico-subthalamic stimulation. (D and E) Quantitative parameters of movement ability. Except for the movement duration, which did not reveal significant changes (n = 4 mice; experiments were repeated twice in each mouse), all of the other locomotor parameters including movement distance, rearing score, and peak velocity were significantly reduced during illumination (light-on versus baseline or light-off; *P < 0.017 under all conditions). (F) Quantitative parameters of asymmetrical movements. Stimulation also caused contralateral motor deficits in all parameters (*P < 0.017 under all conditions). Motor behaviors readily returned to baseline in the light-off state (baseline versus light-off; P > 0.1 under all conditions). All statistical analyses were performed using a nonparametric Wilcoxon signed-rank test with Bonferroni’s post-hoc correction for multiple comparisons. ZI, zona inserta; IC, internal capsule. Refer also to Supplemental Video 1.