Extended Data Fig. 7: In healthy mice, D1R or D2R antagonists affect SPN activity similarly to an acute (but not chronic) loss of dopamine neurons, whereas dopamine receptor agonists have divergent effects from those observed in dopamine-depleted mice.

a–c, Example locomotor trajectories (15-min duration) of mice moving freely within a circular arena (a) and paired example traces of mouse locomotor speed and the mean rate of Ca²⁺ events in dSPNs (b) and iSPNs (c) after administration of saline vehicle or a selective antagonist of D1Rs (SCH23390, 0.2 mg kg⁻¹) or D2Rs (raclopride, 1 mg kg⁻¹). Both drugs reduced locomotion relative to vehicle. P = 10⁻⁴; Wilcoxon signed-rank test; n = 18 mice. d, e, Mean Ca²⁺ event rates in dSPNs (d) and iSPNs (e) as a function of locomotor speed, following administration of saline vehicle, a D1R- or D2R-selective antagonist (0.2 mg kg⁻¹ SCH23390 or 1 mg kg⁻¹ raclopride, respectively) (top) or a D1R- or D2R-selective agonist (1 mg kg⁻¹ SKF81297 or 1 mg kg⁻¹ quinpirole, respectively) (bottom). Rates are normalized to cell population means when mice were at rest (<0.5 cm s⁻¹) after vehicle injection (Methods). Colour shading surrounding each curve denotes s.e.m. f, SPN Ca²⁺ event rates during rest and movement after treatment with a dopamine-receptor antagonist or agonist. The D1R antagonist (SCH23390) reduced dSPN but not iSPN activity. The D2R antagonist (raclopride) increased iSPN but not dSPN activity. Both agonists (quinpirole, SKF81297) reduced activity in both SPN types during rest and movement. *P < 0.05, **P < 5 × 10⁻³, ***P < 5 × 10⁻⁷; Wilcoxon signed-rank test comparing all drug conditions to saline vehicle injection; n = 14 speed bins per mouse in the resting state (<0.5 cm s⁻¹) and 24 speed bins per mouse in the moving state (>0.5 cm s⁻¹); n = 7 Drd1a^cre and 11 Adora2a^cre mice. g, h, Mean Ca²⁺ event rates in dSPNs (g) and iSPNs (h) relative to motion onset (left) and offset (right) following administration of saline vehicle, SCH23390 or raclopride (top), or SKF81297 or quinpirole (bottom). Traces are normalized to cell population means averaged over the time period from −2 to −1 s preceding motion onset. Raclopride increased dSPN (P = 6 × 10⁻¹¹) and iSPN (P = 2 × 10⁻⁹) activation at motion onset. Wilcoxon rank-sum test; comparing 11 time bins for the interval of 0–2 s after motion onset to the baseline periods in each of the 7 Drd1a^cre and 11 Adora2a^cre mice. SCH23390 slightly altered dSPN (P = 0.02) but not iSPN activation (P = 0.4) at motion onset. In Drd1a^cre mice, there were n = 1,917 (vehicle), 134 (SCH23390) and 129 (raclopride) instances of motion onset, whereas in Adora2a^cre mice there were 2,798 (vehicle), 155 (SCH23390) and 233 (raclopride) such instances. Colour shading surrounding each curve denotes s.e.m. i, j, Coactivity of proximal (20–100 μm apart) dSPN (i) or iSPN (j) cell pairs during periods of movement, following administration of saline vehicle, SCH23390 or raclopride (top) or saline, SKF81297 or quinpirole (bottom). Coactivity values are plotted after subtraction of the coactivity values determined for temporally shuffled datasets under the same drug treatment conditions, and then normalized to the values attained for saline administration. Comparing measured values for each drug to those attained with saline; *P < 0.05, **P < 5 × 10⁻³ and ***P < 5 × 10⁻⁷; Wilcoxon signed-rank test; 8 spatial bins of cell–cell separation for each of the n = 7 Drd1a^cre and n = 11 Adora2a^cre mice. d–j, Data are based on the same 7 Drd1a^cre and 11 Adora2a^cre mice. Figure 1a shows the schedule of drug treatments. Data acquired in the 30-min Ca²⁺ imaging sessions after drug administration have been normalized for each mouse to the values determined on the same day during the 30-min Ca²⁺ imaging sessions occurring after saline vehicle administration but before drug treatment.