Extended Data Fig. 6: Restoration of contraversive turning gaits in mice with chronic unilateral striatal dopamine depletion.
From: Basal ganglia–spinal cord pathway that commands locomotor gait asymmetries in mice
a, Strategy for restoring contraversive turning in mice with unilateral striatal dopamine depletion. (b-c) Pre-lesion testing of Chx10Cre mice with Cre-dependent expression of hM3Dq-DREADDs in Gileft. b, Analysis of left vs. right movement preference in the open field c, CNO left vs. CNO right, ***P = 9.0 × 10−4; two-way ANOVA with Tukey’s multiple comparison test; n = 10 mice from two independent experiments. d, Mice with chronic unilateral striatal dopamine depletion exhibited a loss of contraversive (left) turning gaits (–CNO/+6-OHDA). CNO administration (+CNO/+6-OHDA) reversed ipsiversive (right) rotational biases and restored contraversive (left) turning gaits. –CNO/–6-OHDA vs. +CNO/–6-OHDA, ***P < 1.0 × 10−15; –CNO/–6-OHDA vs. –CNO/+6-OHDA, ***P = 8.6 × 10−9; –CNO/+6-OHDA vs. +CNO/+6-OHDA, ***P < 1.0 × 10−15; two-way ANOVA with Tukey’s multiple comparison test; n = 10 mice from two independent experiments. Pre-lesion data (–6-OHDA) is also presented in Fig. 6d. e, Mice with chronic unilateral striatal dopamine depletion exhibited predominantly ipsiversive (right) movement preference. CNO administration at t = 0 reversed ipsiversive rotational biases in a time-dependent manner. Error bands in b and e represent the standard error of the mean. f, CNO left vs. CNO right, *P = 0.017; two-way ANOVA with Tukey’s multiple comparison test; n = 10 mice from two independent experiments. g, Strategy for testing the efficacy PnO-Vglut2contra neurons in restoring contraversive turning in mice with chronic unilateral striatal dopamine depletion. h, Optogenetic stimulation of PnO-Vglut2contra neurons restored straight locomotion at 5 Hz and 10 Hz and contraversive turning at 20 Hz and 40 Hz. i, Mock vs. 20 Hz, *P = 0.021; Mock vs. 40 Hz, *P = 0.029; one-way repeated measures ANOVA with Tukey’s multiple comparison test; n = 4 mice from one experiment. j, Example trajectories associated with mock or 1-s ChR2 stimulation at 10 Hz or 40 Hz. k, Trial-by-trial analysis of angular velocity. n = 4 mice from one experiment. Box-and-whisker plots in c, d, f, and i give the median, the 25th and 75th percentiles, and the range.
