Fig. 4: TS dopamine facilitates threat avoidance and prediction.
From: Dopamine in the tail of the striatum facilitates avoidance in threat–reward conflicts
a, Ablation of dopamine neurons (DA ablation) with 6-OHDA. The white represents tyrosine hydroxylase (TH). Scale bars, 1 mm. b, The avoidance rate was lower in mice with DA ablation in the more posterior striatum (R = 0.83, P = 3.1 × 10−5, Pearson’s correlation coefficients, n = 18 animals). c, The returning points that each animal reached in each trial. d, Left: the avoidance rate in control and DA ablation mice in days 1–3. The average avoidance rates in DA ablation mice were significantly lower than control mice (P = 0.022, control versus ablation mice, two-sided t-test; P = 0.016, control mice; P = 0.45, ablation mice, control versus monster sessions, paired two-sided t-test, n = 6 animals each). Right: time course of avoidance rate in control and TS-DA ablation mice. TS-DA ablation mice succeeded in reward acquisition from the first trial of day 1 (first trial in day 1 versus first trial in control, χ2 = 6, P = 0.014, chi-squared test). The error bars represent the s.e.m. (binomial). e, Left: the average predictive avoidance in days 1–3 in DA ablation mice was significantly lower than control mice (P = 0.028, control versus ablation mice, two-sided t-test; P = 0.048, control mice; P = 0.088, ablation mice, control versus monster sessions, two-sided paired t-test, n = 6 animals each). Right: time course of predictive avoidance in control and TS-DA ablation mice. The error bars represent the s.e.m. (binomial). f, The escape duration was significantly shorter in monster sessions 1–3 than in control sessions with both control mice (black, P = 2.7 × 10−3, two-sided paired t-test, n = 6) and ablation mice (blue, P = 5.8 × 10−3, paired two-sided t-test, n = 6). The error bars represent the s.e.m. g, The mice with vGluT2 knockout (KO) in dopamine neurons avoided a monster (P = 3.2 × 10−5, control; P = 9.3 × 10−5, KO, control versus monster sessions, paired t-test; P = 0.96, control versus KO, two-sided t-test, n = 6 animals for each). The error bars represent the s.e.m. h, The validation of a DAT inhibitor, GBR12909. Left: AAV9-Syn-GRABDA2m was injected into TS. Dopamine sensor signals were recorded while head-fixed mice were presented with a complex tone. Middle: dopamine responses to tone before (top, ‘pre’) and after (bottom, ‘post’) injection of DAT inhibitor or vehicle (mean ± s.e.m.). The dopamine responses were normalized by the responses to 75 dB of tone in the preinjection session. Right: average dopamine responses to tone (0–1 s). The dopamine sensor signals were significantly higher when the DAT inhibitor was infused in the TS than vehicle (P = 0.011, n = 6 sessions with three animals, two-sided paired t-test). The error bars represent the s.e.m. i, The DAT inhibitor or vehicle was bilaterally injected into TS, and the mice were tested in the monster paradigm with a small monster for one session. The avoidance rate was significantly higher with the DAT inhibitor in TS than with the vehicle (P = 0.014, vehicle versus DAT inhibitor, two-sided t-test; P = 0.79, control mice; P = 0.19, DAT inhibitor mice, control versus monster sessions, two-sided paired t-test, n = 6 animals each). The monster icons indicate monster sessions and the circle icons indicate no monster sessions. The error bars represent the s.e.m. *P < 0.05.
