Extended Data Fig. 3: Decrease of predictive avoidance with TS dopamine ablation.
From: Dopamine in the tail of the striatum facilitates avoidance in threat–reward conflicts
(a) Extent of bilateral ablations of dopamine axons with 6OHDA examined by immunohistochemistry with anti-tyrosine hydroxylase (TH) antibody. Ablation areas are marked with red shading, with overlapping shading from ablation mice (n = 6). More densely overlapping areas have redder shading. Ablation areas are marked on the nearest reference slice (Paxinos and Franklin, 2019). (b) TS dopamine ablation did not impact on reward acquisition behaviors in a control session before monster introduction (left, failure of reward acquisition rate, p = 0.54, student t-test, control vs. TS-dopamine ablation; center, latency to enter the monster arena, p = 0.26, two-sided student t-test, control vs. TS-dopamine ablation; right, latency to obtain reward, p = 0.26, two-sided student t-test, control vs. TS-dopamine ablation, n = 6 each). (c) Escape duration was significantly shorter in monster sessions than in control sessions with both control mice (black, p = 0.026, two-sided paired t-test) and ablation mice (blue, p = 0.043, two-sided paired t-test). Ablation mice escaped from the monster as quick as control mice (p = 0.11, two-sided t-test). (d) Predictive avoidance in control and ablation mice was compared. The rate of predictive avoidance gradually increased in control mice but not in DA ablation mice (p = 0.012, control; p = 0.053, ablation, regression coefficient of the predictive avoidance rate with trials, two-sided t-test; p = 0.012, control vs. ablation, two-sided t-test, n = 6 animals for each). (e) Time-course of reactive avoidance in control and TS dopamine ablation mice. Error bars, SEM (binomial). The average reactive avoidance in Day 1-3 of DA ablation were significantly lower than control mice (p = 0.036, control vs ablation mice, two-sided t-test; p = 0.049, control mice; p = 0.26, ablation mice, control vs monster sessions, two-sided paired t-test, n = 6 animals each). (f) The average entry latency in Day 1-3 of DA ablation were slightly shorter than control mice (left, p = 0.058, control vs ablation mice, two-sided t-test; p = 0.067, control mice; p = 0.13, ablation mice, control vs monster sessions, two-sided paired t-test, n = 6 animals each). The average trigger latency in Day 1-3 of DA ablation were significantly shorter than control mice (right, p = 0.042, control vs ablation mice, two-sided t-test; p = 0.059, control mice; p = 0.10, ablation mice, control vs monster sessions, two-sided paired t-test, n = 6 animals each). (g) DAT inhibitor or vehicle was bilaterally injected into TS, and mice were tested in the monster paradigm with a small monster for 1 session (predictive avoidance, p = 0.21, vehicle vs DAT inhibitor, two-sided t-test; p = 1, control mice; p = 0.1, DAT inhibitor mice, control vs monster sessions, two-sided paired t-test, n = 6 animals each, reactive avoidance, p = 0.10, vehicle vs DAT inhibitor, two-sided t-test; p=na, control mice; p = 0.34, DAT inhibitor mice, control vs monster sessions, two-sided paired t-test, n = 6 animals each.). (h) Avoidance was increased when DAT inhibitor was bilaterally injected in TS before monster Day 2-3, after mice experienced monster in Day 1 (avoidance rate, p = 0.005, F(2,20) = 7.02, 2-way ANOVA drug × session interaction; p = 0.038, two-sided t-test; predictive avoidance rate, p = 0.34, F(2,20) = 0.43, 2-way ANOVA drug × session interaction; reactive avoidance rate, p = 0.002, F(2,20) = 8.42, 2-way ANOVA drug × session interaction; p = 0.019, two-sided t-test, n = 6 animals for each). *P < 0.05.
