Extended Data Fig. 2: Dorsolateral DA dynamics during lever pressing and in lesioned mice.

a, Experimental design: extracellular DA levels are monitored in the dorsolateral striatum contralateral to the limb used to press the lever using fiber photometry of the red DA sensor rDA1m virally expressed in striatal neurons. b, Fiber optic placement in dorsolateral striatum across N = 8 mice. c, Heat plot of average rDA1m fluorescence aligned to water delivery (dashed white line) across N = 8 mice, each showing a brief, short-latency, reward-related increase in fluorescence. d, rDA1m fluorescence signal (top) and lever trajectory (bottom) aligned to reward omission (dashed blue line). Session-average for each mouse (N = 8) shown in gray, and population mean ± SEM shown in red (top) and blue (bottom). Dashed green line indicates time that reward threshold is crossed. Dashed red line depicts mean rDA1m signal to reward delivery, as shown in Fig. 2c. Note the relative dip in fluorescence at reward omission, and the absence of consistent elevations in DA prior to deflection of the lever. e, Example single-trial rDA1m fluorescence signals (each in various shades of gray) aligned to press onset (dashed line). Note the presence of large subsecond fluctuations in DA while mice are immobile prior to press onset, and the absence of consistent elevations in DA before or at press onset. f, Average rDA1m signal aligned to press onset (dashed line) for each of N = 8 mice (solid gray traces) and across entire population ( ± SEM; in red). Note the net tendency for DA levels to dip slightly prior to and during press execution. g, Scatter plot of peak press velocity (top) or press amplitude (bottom) vs. rDA1m signal 1 s prior to press onset for all recorded presses (n = 1,702 across 8 mice). Regression line (black), correlation coefficient r and statistical significance for slope being different from 0 (F-test). h, Same as g for rDA1m signal 0.5 s prior to press onset. i, Same as g for rDA1m signal at press onset. j, Example subsecond rDA1m fluorescence signals for 3 mice across different conditions: pre-lesion + saline treatment (black), pre-lesion + raclopride treatment (gray), post-lesion + saline treatment (red) and post-lesion + levodopa treatment (green). k, Mean ± SEM rDA1m fluorescence aligned to peak acceleration of locomotion on a treadmill pre-lesion (black), post-lesion (red) and post-lesion with levodopa treatment (green). Note the absence of net movement-aligned changes rDA1m fluorescence post-lesion, consistent with the absence of movement artefacts and the complete loss of phasic DA signaling, including following levodopa treatment.

Source data