Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning

TY - JOUR

T1 - Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning

AU - Gao, Zhenyu

AU - Proietti-Onori, Martina

AU - Lin, Zhanmin

AU - Ten Brinke, Michiel M

AU - Boele, Henk-Jan

AU - Potters, Jan-Willem

AU - Ruigrok, Tom J H

AU - Hoebeek, Freek E

AU - De Zeeuw, Chris I

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/2/3

Y1 - 2016/2/3

N2 - 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.

AB - 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.

U2 - 10.1016/j.neuron.2016.01.008

DO - 10.1016/j.neuron.2016.01.008

M3 - Article

C2 - 26844836

SN - 0896-6273

VL - 89

SP - 645

EP - 657

JO - Neuron

JF - Neuron

IS - 3

ER -