Fig. 1: Opponent signaling of force direction by two distinct DA neuron populations.

a Force monitoring during a stimulus-reward task. b Representative task and spontaneous force from a trained mouse (Supplemental Movie 1). c Spontaneous movements were present at all stages of training (Two-way RM ANOVA, Effect of Direction: F(1,9) = 21.6, p = 0.0012, no effect of training F(2,18) = 3.4, p = 0.054, Interaction: F(12,18) = 14.04, p = 0.0002, n = 10 mice. Spontaneous forward movements were more common at all stages of training (p < 0.0001). d VTA dopamine (DA) neurons were identified by optogenetic tagging in DAT-Cre mice, confirmed by GFP and TH co-expression. e Opponent signaling of force direction by two classes of DA neuron (Two-way ANOVA, Interaction: F(1,472) = 1218, p < 0.0001). f Forward and Backward DA populations comprised ~50% of all DA neurons. g Distributions of cross-correlation lag for Forward and Backward DA neurons with their preferred force direction. h Left: Forward DA neurons were activated during forward movements (n = 341 neurons). Right: the same neurons (same sorting order) were suppressed during backward movements. i Representative Forward DA neuron (linear regression; Forward R2 = 0.73, p = 0.001, Backward R2 = 0, p = 0.89). j Forward DA population tuning (linear regression; Forward R2 = 0.97, p < 0.0001, Backward R2 = 0.81, p = 0.0003, n = 341 neurons). k Left: Backward DA neurons were suppressed during spontaneous forward movements (n = 133 neurons). Right: same neurons (same sorting order) were activated during spontaneous movements backward. l Representative Backward DA neuron (linear regression; Forward R2 = 0.17, p = 0.22, Backward R2 = 0.81, p = 0.0004). m Backward DA population tuning (linear regression; Forward R2 = 0.63, p = 0.0061, Backward R2 = 0.88, p < 0.0001, n = 133 neurons). n DA concentration using firing rate (FR) and reuptake dynamics (K, Vmax) to predict force exertion. o Modeled DA concentration from observed Forward and Backward DA activity recapitulates force profiles (n = 341 Forward DA, 133 Backward DA; 4455 forward, 5313 backward movements). Error bars represent SEM. Source data are provided as a Source Data file.