Reward-driven cerebellar climbing fiber activity influences both neural and behavioral learning

The cerebellum plays a key role in motor coordination and learning. In contrast with classical supervised learning models, recent work has revealed that CFs can signal reward-predictive information in some behaviors. This raises the question of whether CFs may also operate according to the principles of reinforcement learning. To test how CFs operate during reward-guided behavior, and evaluate the role of reward-related CF activity in learning, we have measured CF responses in Purkinje cells of the lateral cerebellum during a Pavlovian task using 2-photon calcium imaging. Specifically, we have performed multi-stimulus experiments to determine whether CF activity meets the requirements of a reward prediction error (rPE) signal for transfer from an unexpected reward to a reward-predictive cue. We find that once CF activity is transferred to a conditioned stimulus, and there is no longer a response to reward, CFs cannot generate learned responses to a second conditioned stimulus that carries the same reward prediction. In addition, by expressing the inhibitory opsin GtACR2 in neurons of the inferior olive, and optically inhibiting these neurons across behavioral training at the time of unexpected reward, we find that the transfer of CF signals to the conditioned stimulus is impaired. Moreover, this optogenetic inhibition also impairs learning, resulting in a deficit in anticipatory lick timing. Together, these results indicate that CF signals can exhibit several characteristics in common with the rPEs that have been observed during reinforcement learning, and that the cerebellum can harness these reward-related learning signals to generate accurately timed motor behavior.