Positive feedback of efferent copy via pontine nucleus facilitates cerebellum-mediated associative learning

The cerebellum is critical for motor coordination and learning. However, the role of feedback circuitry in this brain region has not been fully explored. Here, we characterize a nucleo-ponto-cortical feedback pathway in classical delayed eyeblink conditioning (dEBC) of rats. We find that the efference copy is conveyed from the interposed cerebellar nucleus (Int) to cerebellar cortex through pontine nucleus (PN). Inhibiting or exciting the projection from the Int to the PN can decelerate or speed up acquisition of dEBC, respectively. Importantly, we identify two subpopulations of PN neurons (PN1 and PN2) that convey and integrate the feedback signals with feedforward sensory signals. We also show that the feedforward and feedback pathways via different types of PN neurons contribute to the plastic changes and cooperate synergistically to the learning of dEBC. Our results suggest that this excitatory nucleo-ponto-cortical feedback plays a significant role in modulating associative motor learning in cerebellum. © 2023 The Author(s).