Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning

Zhenyu Gao, Martina Proietti Onori, Zhanmin Lin, Michiel Brinke, Henk-jan Boele, Jan-willem Potters, Tom Ruigrok, Freek Hoebeek, Chris de Zeeuw

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Abstract

Closed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning.
Original languageUndefined/Unknown
Pages (from-to)645-657
Number of pages13
JournalNeuron
Volume89
Issue number3
DOIs
Publication statusPublished - 2016

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