A Nucleo-Ponto-Cortical Circuit Facilitates Cerebellum-Mediated Associative Learning Via Excitatory Feedback of Efference Copy

Abstract

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 characterized a nucleo-pontine-cortical feedback pathway in classical delayed eyeblink conditioning (dEBC). We found that the efference copy is conveyed from the interposed nucleus (Int) to cerebellar cortex through pontine nucleus (PN). Inhibiting or exciting the projection from Int to PN can decelerate or speed up acquisition of dEBC. We uncovered two subpopulation of PN neurons which convey and integrate the feedback signals with feedforward sensory signals. In a series of novel behavioral experiments, we also showed that the feedforward and feedback pathways via different types of PN neurons are functionally distinct but contribute to the plasticity synergistically to facilitate learning of dEBC. Our results suggest that this excitatory nucleo-ponto-cortical feedback plays a significant role in modulating associative motor learning in cerebellum.