Extended Data Fig. 7: Prolonged chemogenetic inhibition of PFCPu neurons rescued locomotion in PD model mice up to 10 days later.
From: Targeting thalamic circuits rescues motor and mood deficits in PD mice
a, TH staining in CPu of saline control (left) or 6-OHDA-injected PD model (right) mice. b, Open field test using saline control and PD model mice 30 days after 6-OHDA injections (n = 11 saline, n = 8 PD model mice). c, Representative traces and evoked EPSC amplitudes recorded in CPu neurons receiving PF input from control and PD model mice (Control: n = 15 neurons (5, 5, 5), PD: n = 16 neurons (5, 6, 5) from 3 mice each). d, PFCPu inhibition in PD model mice by injecting a retrograde RVdGL-Cre in CPu, Cre-dependent hM4Di-mCh in PF, and 6-OHDA in SNc. e-j, Open arena behavior protocol using two different manipulation strategies starting from 14 days after 6-OHDA injections (e). For single manipulation experiments, total distance during a 20-min open arena test was measured prior to the C21 injection (Baseline), or 40 min and 3 days after one C21 injection (Test) (Baseline: n = 20 WTmCh, n = 16 PDmCh, n = 20 PDhM4Di mice; 40 min and 3 days: n = 14 WTmCh, n = 12 PDmCh, n = 14 PDhM4Di mice) (f). Saline was injected 40 min before the baseline session. For prolonged manipulation experiments, total distance, number of movements, and moving time (g-j) during tests were measured 7 days and 10 days after the 3-day prolonged C21 protocol (Day 7 and Day 10: n = 20 WTmCh, n = 16 PDmCh, n = 20 PDhM4Di mice). In panels h and i, baseline data plotted from panel f. WTmCh mice were injected with a retrograde RVdGL-Cre injected in CPu, Cre-dependent mCh in PF, and saline in SNc. Day 7 data related to Fig. 4b (j). Data are presented as mean ± SEM; **P < 0.01, ***P < 0.001. NS, not significant. Two-tailed unpaired t test (b, c), and one-way ANOVA followed by Bonferroni post-hoc test (f, g). P = 0.033 (b), P = 0.004 (c), Baseline: F = 17.77, P < 0.0001, WTmCh vs. PDmCh t = 5.26, PDmCh vs. PDhM4Di t = 0.006, 40 min after C21: F = 10.7, P = 0.0002, WTmCh vs. PDmCh t = 4.35, PDmCh vs. PDhM4Di t = 3.67, 3 days after C21: F = 15.35, P < 0.0001, WTmCh vs. PDmCh t = 5.44, PDmCh vs. PDhM4Di t = 2.06 (f), Day 7: F = 9.46, P = 0.0003, WTmCh vs. PDmCh t = 4.05, PDmCh vs. PDhM4Di t = 3.57, Day 10: F = 10.72, P = 0.0001, WTmCh vs. PDmCh t = 4.37, PDmCh vs. PDhM4Di t = 3.69 (g)
