Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning.

Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning.
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DOI:
10.1016/j.neuron.2016.01.008
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发表时间:
2016-02-03
期刊:
影响因子:
16.2
通讯作者:
De Zeeuw CI
De Zeeuw CI
中科院分区:
医学1区
文献类型:
--
作者:
Gao Z;Proietti-Onori M;Lin Z;Ten Brinke MM;Boele HJ;Potters JW;Ruigrok TJ;Hoebeek FE;De Zeeuw CI

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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. Cerebellar nuclei provide modular corollary discharge to the cerebellar cortex Nucleocortical afferents have unique molecular and ultrastructural features Eyeblink conditioning induces structural plasticity of nucleocortical mossy fibers Nucleocortical afferents amplify the amplitude of conditioned eyeblink responses The role of the closed-loop circuitry between cerebellar nuclei and cortex is unknown. Gao et al. show that nucleocortical inputs provide corollary discharges to the granular layer, are plastic upon eyeblink conditioning, and amplify the amplitude of conditioned responses.