Fig. 4. Dopaminergic genetic subtypes display different responses to rewards and aversive stimuli.
a, Mouse running on treadmill during fiber photometry while receiving unexpected rewards and air puffs. b, Schematic of fiber photometry recording strategy. c, Example recordings for each subtype studied, showing fluorescence traces (ΔF/F), mouse velocity, acceleration, licking and reward (left) or air puff (right) delivery times. Isosbestic controls in light blue, same scale as ΔF/F traces. Reward and air puff examples for each subtype are from the same recording. d, ΔF/F averages triggered on reward delivery times for all recordings of each subtype and DAT. Isosbestic control in light blue, same scale as ΔF/F average. Acceleration shown in gray in background (scale bar, 0.2 m s−2). Shaded regions denote mean ± s.e.m. across recordings. Heat maps show triggered average for each recording, sorted by size of reward response. Vglut2 mice = 11, n = 28 recordings; Calb1 mice = 8, n = 17 recordings; Anxa1 mice = 8, n = 51; DAT mice = 11, n = 63 recordings. See Extended Data Fig. 8h,i for averages per mouse. e, Licking average triggered on reward delivery times for all recordings of each subtype and DAT (same as d). Shaded areas denote mean ± s.e.m. across recordings. Heat map shows triggered average for each recording, sorted as in d. f, ΔF/F averages triggered on air puff delivery times for all recordings of each subtype and DAT. Isosbestic control in light blue, same scale as ΔF/F average. Acceleration shown in gray in background (scale bar, 0.2 m s−2). Shaded regions denote mean ± s.e.m. Heat map shows triggered average for each recording, sorted by reward size as in d,e. Vglut2 mice = 12, n = 29 recordings; Calb1 mice = 8, n = 17 recordings; Anxa1 mice = 8, n = 57 recordings; DAT mice = 11, n = 69 recordings. g, Average reward and air puff responses for each subtype (integral of fluorescence in a 0.5-s window after stimulus minus integral in 0.5 s before stimulus). Error bars denote mean ± s.e.m. across recordings. Means (m) and P values for reward: Vglut2 mice = 7.9 normalized ΔF/F s, P = 2 × 10−5; Calb1 mice = 12.4, P = 0.001; Anxa1 mice = −0.5, P = 0.1 (NS); DAT mice = 5.9, P = 9 × 10−7. Means (m) and P values for air puff: Vglut2 mice = 15.8, P = 1 × 10−5; Calb1 mice = 5.3, P = 0.007, Anxa1 mice = −3.7, P = 4 × 10−8; DAT mice = 5.3, P = 0.02 (two-sided Wilcoxon signed-rank test with Bonferroni correction). Same n as d,f. h, Reward versus air puff responses for all recordings of each subtype and DAT. X shows mean for each subtype. Shaded regions are areas representing greater air puff than reward response (for Vglut2) or greater reward versus air puff response (for Calb1). i, Comparison of responses to small versus large rewards for each subtype. Error bars denote mean ± s.e.m. Mean difference (m) and P values: Vglut2 mice = 0.9 normalized ΔF/F s, P = 0.6 (NS); Calb1 mice = 3.9, P = 9 × 10−3; Anxa1 mice = 0.04, P = 1 (NS); DAT mice = 1.9, P = 8 × 10−5(two-sided paired Wilcoxon signed-rank test with Bonferroni correction). Vglut2 mice = 11, n = 25 recordings; Calb1 mice = 6, n = 14 recordings; Anxa1 mice = 8, n = 42 recordings; DAT mice = 10, n = 55 recordings. j, Reward response mapped onto recording locations for each subtype and DAT. Locations from the body or the tail of the striatum were collapsed into a single brain section. To reduce overlap, locations were shifted a random amount between ±0.4 mm mediolaterally. See Extended Data Fig. 8j,k for an expanded version of this panel without shifts or collapsing slices together. k, Same as j but for air puff response. l, Comparison of reward and air puff response for Calb1 and Anxa1 recordings only from a region of striatum where their axons overlap, dashed red circle. Isosbestic control in blue. Shaded regions denote mean ± s.e.m. across recordings. Calb1 mice = 4, n = 9 recordings; Anxa1 mice = 5, n = 13 for rewards, n = 17 for air puffs. acc, acceleration; vel, velocity.