Fast and slow learning mediated by distinct climbing fiber signals

Learning on both fast and slow timescales is required to enable us to adapt to a dynamic environment. Whether the mechanisms mediating fast and slow learning are implemented by the same, or different, circuit elements remains an important open question. Learning involving the cerebellum is known to be driven primarily by instructive climbing fiber inputs to Purkinje cells, but the dynamics of climbing fibers across learning on fast and slow timescales are not known. It is unclear if climbing fibers encode the same or different instructive signals at different stages of learning, and whether learning-related changes in climbing fiber encoding properties across timescales are driven by the same or distinct mechanisms. We addressed this problem using longitudinal 2-photon calcium imaging of climbing fiber activity across multiple cerebellar lobules as mice learned to execute a visuomotor integration task - slow learning - and then rapidly adapted to a new sensorimotor coupling - fast learning. Instructive signals are spatially segregated in trained mice: Lobule V preferentially encodes movement predictively, while Lobule simplex preferentially receives reward-related feedback. Moreover, the encoding of sensorimotor and reward-related instructive signals is dynamic on both slow and fast timescales: movement-related activity emerges over the course of training, while reward-related activity progressively diminishes as mice become experts but re-emerges specifically in Lobule simplex when rewards become scarce. Finally, while the same climbing fiber inputs can change on both timescales, the magnitude and spatial organization of slow changes are not related to fast changes. Thus, climbing fiber input can carry distinct instructive signals on different timescales - a multiplexing of teaching signals that may underlie the cerebellums capacity to both acquire and refine motor behaviour.