Extended Data Fig. 2: Context-dependent effect of iSPN stimulation.

a, c. Effect of devaluating one motor program by extinction. An example session from one mouse showing the effects of iSPN stimulation on the left (a) or right (c) hemisphere before (pre-extinction, top) and after (post-extinction, bottom) devaluation of the right port. Each dot represents licking either to the left (blue) or right (red). Trials (rows) are sorted by being no stimulation (black) and stimulation trials (light blue). Only trials with licking cued to the port contralateral to optogenetic stimulation (right in a, left in c) are shown. b, d. Percentages of each outcome type for pre- (black, left) and post- (purple, right) extinction optogenetic stimulation trials (stim, light blue) and control trials (no stim, black). Outcomes are color-coded grey (correct), green (incorrect), and orange (miss) (n = 5 mice). The selection of the incorrect port following optogenetic stimulation of iSPN on the right striatum significantly decreased after extinction (P<0.0125, one-tailed t-test), whereas it remained the same for iSPN stimulation on the left (P = 0.65, one-tailed t-test). e. Effect of bilateral iSPN stimulation. Summary plots for the outcomes for no stimulation (black) and stimulation (light blue) trials, during left- (center) and right- (right) cued trials (n = 5 mice). Optogenetic stimulation significantly decreased the correct outcome rate and increased the miss outcome rate but did not change the incorrect outcome rate (**P < 0.001, two-tailed t-test; n.s.: P > 0.05). f. left, We trained a group of mice to only lick to the left spout, while still having access to both spouts. Right iSPN stimulation in these mice failed to induce licking of the right spout, supporting that stimulation-induced licking is not a hardwired motor program. right, Stimulation decreased correct outcome rate and increased the miss outcome rate, but failed to increase incorrect outcome rate (i.e. the rate of licking to the right spout which the mice were never trained to lick) (**P < 1 × 1e−8, two-tailed t-test; n.s.: P > 0.05). g. As in panel f for left VLS iSPN stimulation (*P < 0.05, two-tailed t-test; n.s.: P > 0.05). h. In mice trained on the main two-spout task, we also observed that iSPN stimulation during the inter-trial-interval (ITI), when mice rarely licked, induced ipsiversive licking although this effect emerged only after multiple stimulation sessions. Plots showing change in probability of licking after optogenetic stimulation during the ITI relative to control trials (n = 10 mice for 1^st and 2^nd session, n = 9 mice for 3^rd session). Stimulation caused ipsilateral licking from 2^nd session onward, and weakly suppressed contralateral licking relative to baseline (***P < 1x1e-4, **P < 0.005, *P < 0.05).