title: Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning.
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.
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands. Electronic address: z.gao@erasmusmc.nl.
authors: Zhenyu
authors: Z
authors: Gao
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
authors: Martina
authors: M
authors: Proietti-Onori
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
authors: Zhanmin
authors: Z
authors: Lin
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
authors: Michiel M
authors: MM
authors: Ten Brinke
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
authors: Henk-Jan
authors: HJ
authors: Boele
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
authors: Jan-Willem
authors: JW
authors: Potters
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
authors: Tom J H
authors: TJ
authors: Ruigrok
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
authors: Freek E
authors: FE
authors: Hoebeek
authors: Department of Neuroscience, Erasmus MC, 3015 CN Rotterdam, the Netherlands; Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts & Sciences (KNAW), 1105 BA Amsterdam, the Netherlands. Electronic address: c.dezeeuw@erasmusmc.nl.
authors: Chris I
authors: CI
authors: De Zeeuw
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology; D001767:Blinking / Q000502:physiology*; D002525:Cerebellar Cortex / Q000502:physiology*; D002529:Cerebellar Nuclei / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D009412:Nerve Fibers / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology*; D062308:Optogenetics