Dissociable patterns of dopamine dynamics and causal contributions to stimulus-response behaviors across striatal subregions

Striatal dopaminergic dynamics exhibit regional variation, yet are usually studied in isolation, with interpretations often extrapolated to the striatum as a whole. Here we used fiber photometry to characterize DA dynamics across the nucleus accumbens, dorsomedial, and dorsolateral striatum in parallel in mice performing a striatum-dependent stimulus-response (S-R) learning task. We found that transients in all regions varied dynamically across task events but differed significantly across regions in their timing of peak responding, presence of pre-choice ramping, and stability across learning. Next, manipulations of reward probability revealed that DA transients in all regions tracked reward delivery and omission, but not choice. Lastly, we used inhibitory chemogenetics to test the necessity of these signals for cognition, revealing that nigrostriatal DA, but not mesolimbic striatal DA, was necessary for the acquisition of S-R contingencies. These findings demonstrate heterogeneity of DA signals across the striatum and reveal their distinct, causal roles in cognition.