Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice

Climbing fiber inputs to Purkinje cells are thought to play a teaching role by generating the instructive signals that drive cerebellar learning. To investigate how these instructive signals are encoded, we recorded the activity of individual climbing fibers during cerebellar-dependent eyeblink conditioning in mice. Our findings show that climbing fibers signal both the unexpected delivery and the unexpected omission of the periocular airpuff that serves as the instructive signal for eyeblink conditioning. In addition, we report the surprising discovery that climbing fibers activated by periocular airpuffs also respond to stimuli from other sensory modalities, if those stimuli are novel or if they predict that the periocular airpuff is about to be presented. This pattern of climbing fiber activity is strikingly similar to the responses of dopamine neurons during reinforcement learning, which have been shown to encode a particular type of instructive signal known as a temporal difference prediction error.