Purkinje cells in Crus I and II encode the visual stimulus and the impending choice as monkeys learn a reinforcement...

Evidence implicates the cerebellum in motor learning and performance, and relatively simple sensorimotor associations such as classical conditioning. However, little is known about how Purkinje cells encode more complex associations, such as arbitrary stimulus-response mappings. To address this, we recorded from Crus I/II Purkinje cells while two male macaques learned to associate novel fractal cues with left- or right-hand bar release. Here we show that as learning progresses, the simple spike activity of individual neurons becomes more selective for stimulus-response associations, with selectivity for left or right association developing closer to the appearance of visual stimuli. Initially, most neurons respond to both associations, irrespective of the identity of the stimulus and the associated movement, but as learning advances, more neurons distinguish between specific stimulus-hand associations. Moreover, complex spikes, which respond after the appearance of the stimuli, decrease their activity as the monkeys learn the task, suggesting that climbing-fiber activity encodes higher-order sensorimotor associations beyond mere error signaling. Using a linear decoder, we found that in early learning stages, the visual stimulus can be decoded only when the choice can also be decoded. As learning progresses, the visual stimulus is decoded earlier than the choice. A simple model can replicate the observed Purkinje cell signals in both the early and late learning stages.Significant Statement The cerebellum is traditionally associated with motor learning, yet its contribution to complex stimulus-response associations remains unclear. Recording Purkinje cells in Crus I/II as monkeys learned visuomotor associations, we found that activity evolves from reactive to predictive with learning. Simple spikes encode the upcoming choice progressively earlier, while complex spikes shift from a reactive response to the stimulus during early learning to a predictive signal before movement. Thus, cerebellar populations integrate sensory and motor inputs to generate anticipatory, decision-related activity.