Differential contributions of striatal dopaminergic pathways to visuomotor conditional learning

Rationale: Midbrain dopamine (DA) neurons project principally towards the striatum, serving as key regulators of movement, motivation, and cognition. Different striatal dopaminergic (DA) pathways may regulate different aspects of cognition. Objectives: We investigated how different striatal DA pathways contribute to a known function of the striatum, visuomotor conditional learning. Methods: Using fiber photometry, we recorded DA transients in these regions as mice learned the touchscreen Visuo-Motor Conditional Learning task. Results: DA transients in all regions dynamically tracked task events, but differed in the timing of peak responses and ramp-like activity preceding a choice, indicating region-specific temporal dynamics across learning. Manipulations of reward probability revealed DA transients in all regions during reward delivery and omission that are consistent with an interpretation in terms of reward prediction error. Thus, DA dynamics in all regions could indicate involvement in visuomotor conditional learning. Therefore, to determine whether nigrostriatal or mesolimbic DA is necessary for learning, we chemogenetically inhibited DA striatal afferents, revealing that only DLS-projecting nigrostriatal DA, and not NAc-projecting mesolimbic striatal DA, was necessary for learning the task. Conclusion: These findings demonstrate functional heterogeneity of aspects of striatal DA signaling, and selective causal roles in the learning of visuomotor conditional learning.