Fig. 7: TS dopamine actions onto D1 and D2 neurons.
From: Dopamine in the tail of the striatum facilitates avoidance in threat–reward conflicts
a, TS dopamine ablation mice were injected with D1R agonist (SKF-38393) or D2R agonist (quinpirole) before each session for day 1–3 monster sessions. The control mice received vehicle injection during surgery and test days. b, The avoidance was increased by D1R agonist injection in a dose-dependent manner on day 1 (P = 1.2 × 10−4, F(2,17) = 21.31, one-way ANOVA; P = 0.041, 0 µg versus 0.5 µg, P = 3.7 × 10−6, 0 µg versus 5 µg, two-sided t-test) and on the first trial (P = 1.0 × 10−3, 0 µg versus 5 µg, χ2 = 12, chi-squared test) and then gradually decreased (P = 1.3 × 10−3, 5 µg, P = 0.24, 0.5 µg, P = 0.80, 0 µg, regression coefficient of the avoidance rate with trials, two-sided t-test), similar to control mice (P = 6.1 × 10−3, regression coefficient of the avoidance rate with trials, control, two-sided t-test). n = 6 animals for each. The error bars represent the s.e.m. c, Avoidance was recovered by the D2R agonist in a dose-dependent manner on day 1 (P = 1.2 × 10−4, F(2,17) = 13.60, one-way ANOVA; P = 7.0 × 10−3, 0 µg versus 0.2 µg; P = 2.2 × 10−5, 0 µg versus 2 µg, two-sided t-test) and on the first trial (P = 1.0 × 10−3, 0 µg versus 2 µg, χ2 = 12, chi-squared test) and gradually decreased or increased across days depending on the agonist doses (P = 5.1 × 10−3, F(2,30) = 6.50, session × dose interaction, two-way repeated measures ANOVA; P = 0.11, 2 µg, P = 0.022, 0.2 µg, P = 0.80, 0 µg, regression coefficient of the avoidance rate with trials, two-sided t-test). n = 6 animals for each; mean ± s.e.m. d, A schematic for simultaneous optogenetic activation of dopamine axons and fluorometry recording of GCaMP signals from either D1 or D2 neurons in the TS. Head-fixed mice were presented with a complex visual and auditory stimulus in trials with (‘stim’) or without (‘no stim’) concurrent optogenetic stimulation. e, Dopamine sensor (GRABDA3m) signals at a sensory stimulus in the same task as d. The time of optogenetic stimulation (0–4 s) is shown in gray. n = 6 animals; mean ± s.e.m. f, Left: D1 neuron response patterns in trials with or without optogenetic stimulation on the first day of the sensory experience in all animals (mean ± s.e.m. (top), each animal (bottom)). Right: the average D1 neuron responses (0–4 s) in stimulated trials were significantly higher than in nonstimulated trials in ChrimsonR-expressing mice (P = 1.1 × 10−3, t = 6.65, paired two-sided t-test, ChrimsonR mice; P = 0.85, t = 0.19, two-sided paired t-test, control mice; P = 0.016, t = 2.88, two-sided t-test, control versus ChrimsonR mice, n = 6 animals each). g, Left: D1 neuron response patterns in nonstimulated trials on the first and second day of the sensory experience in all animals (mean ± s.e.m. (top), each animal (bottom)). Right: average D1 neuron responses (0–4 s) significantly decreased on the second day compared with responses on the first day in control mice but not in ChrimsonR mice (P = 0.012, t = −3.85, two-sided paired t-test, control mice; P = 0.46, t = −0.79, two-sided paired t-test, ChrimsonR mice; P = 0.014, t = 2.96, two-sided t-test, control versus ChrimsonR mice, n = 6 animals each). h, Left: same format as f but for D2 neurons. D2 neuron responses (0–4 s) did not significantly change by optogenetic stimulation (control mice, P = 0.93, t = −0.09; ChrimsonR mice, P = 0.24, t = −1.32, two-sided paired t-test; P = 0.24, t = −1.23, two-sided t-test, difference in control versus ChrimsonR mice, n = 6 animals each). i, Left: same format as g but for D2 neurons. D2 neuron responses (0–4 s) in nonstimulated trials were not significantly different between the first and second days (control mice, P = 0.42, t = −0.86; ChrimsonR mice, P = 0.87, t = −0.16, two-sided paired t-test; P = 0.67, t = 0.42, two-sided t-test, difference in control versus ChrimsonR mice, n = 6 animals each). In the box plots, the middle lines are the median, the edges are the 25th and 75th percentiles, the whiskers are the most extreme data points not considered as outliers and the crosses are outliers. *P < 0.05.
