Predictive and instructive cerebellar encoding of dopamine reward drives motivated behavior

ABSTRACT Learning motivated behaviors requires both anticipating rewarding outcomes and reinforcing the actions that yield them. Although cerebellar activity encodes natural rewards like water and food, it also coordinates the physical movements of eating and drinking. To disentangle reward from consummatory movements, we trained mice to push for delayed dopamine rewards delivered directly into the brain. Via two-photon imaging, we found that many cerebellar granule cells (GrCs) predictively encoded dopamine rewards with sustained activity that terminated upon delivery. GrC activity also “stretched” to match 1- or 2-s intervals before dopamine, thereby linking the action to the expected reward time. By contrast, most cerebellar climbing fibers (CFs) spiked just after dopamine delivery. In mice sequentially trained with both reward types, reward encoding strength for dopamine matched or exceeded that for water, with many individual neurons generalizing across both. Both cell types contributed causally: chronic GrC inhibition disrupted self-stimulation learning, and CF self-stimulation “rewards” drove moderate operant learning in naive animals. Thus, cerebellar input streams use both predictive and instructive codes for dopamine reward that help drive motivated behavior, suggesting deeper cerebellar integration in brain reward prediction networks. Competing Interest Statement The authors have declared no competing interest. Footnotes More control studies, increased sample sizes, longitudinal learning data, numerous additional and refined analyses.