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  • Review Article
  • Published:

Distributed synergistic plasticity and cerebellar learning

Nature Reviews Neuroscience volume 13, pages 619–635 (2012)Cite this article

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An Erratum to this article was published on 15 November 2012

This article has been updated

Key Points

  • The cerebellum is involved in motor learning, yet the precise forms of plasticity that may underlie this form of memory formation are still under debate.

  • Recent advances in mouse transgenics and phenomics have provided new pieces of evidence as to how different forms of plasticity at synaptic and extrasynaptic sites in the cerebellar cortex may act together to mediate particular aspects of motor learning.

  • By systematically reviewing all forms of plasticity in the granule cell network and Purkinje cell network and integrating the behavioural phenotypes that can be observed following manipulation of these forms of plasticity, we propose that plasticity in the cerebellar cortex operates in a distributed and synergistic manner.

  • Mediated mainly by input from the mossy fibres, plasticity in the granular layer may serve to spread diversity of coding, while climbing fibre-guided plasticity in the molecular layer may serve to select the appropriate coding required for the specific spatiotemporal demands of the motor learning paradigm involved.

  • Owing to the distributed and synergistic character of cerebellar cortical plasticity guided by common afferent inputs, there is ample room for compensatory mechanisms so as to warrant the consecutive processes of motor performance, motor learning and motor consolidation.

Abstract

Studies on synaptic plasticity in the context of learning have been dominated by the view that a single, particular type of plasticity forms the underlying mechanism for a particular type of learning. However, emerging evidence shows that many forms of synaptic and intrinsic plasticity at different sites are induced conjunctively during procedural memory formation in the cerebellum. Here, we review the main forms of long-term plasticity in the cerebellar cortex that underlie motor learning. We propose that the different forms of plasticity in the granular layer and the molecular layer operate synergistically in a temporally and spatially distributed manner, so as to ultimately create optimal output for behaviour.

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Figure 1: Molecular mechanisms underlying plasticity in granule cells.
Figure 2: Spreading diversity and setting time windows in the granule cell network.
Figure 3: Molecular mechanisms underlying plasticity in Purkinje cells.
Figure 4: Creating output by selecting input in the Purkinje cell network.

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Change history

  • 15 November 2012

    In figure 3 of this article, the arrows indicating AMPA receptor exocytosis and endocytosis in the postsynaptic neuron should have been red and black, respectively.

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Acknowledgements

We kindly thank the Dutch Organization for Medical Sciences (ZonMw; C.I.D.Z.), Life Sciences (ALW; C.I.D.Z., Z.G. and B.J.v.B.), Senter (NeuroBasic; C.I.D.Z) and Prinses Beatrix Fonds (C.I.D.Z.), and the ERC-advanced, CEREBNET and C7 programs of the European Community (C.I.D.Z.) for their financial support. We also thank F.E. Hoebeek, M. Schonewille, E. Galliano and other laboratory members for valuable discussions.

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  1. Zhenyu Gao and Boeke J. van Beugen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, Erasmus Medical Center, Rotterdam, 3000 DR, The Netherlands

    Zhenyu Gao, Boeke J. van Beugen & Chris I. De Zeeuw

  2. Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts & Sciences (KNAW), Amsterdam, 1105 BA, The Netherlands

    Chris I. De Zeeuw

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  1. Zhenyu Gao
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Glossary

Intrinsic plasticity

Modification of a neuron's intrinsic electrical properties through changes in ion channel expression and properties in the neuron membrane. It can be induced by either neuronal spiking activity or synaptic inputs.

Motor performance

Baseline performance of movements. It corresponds to the absolute amplitude (gain) and timing (phase) values of the movements before any training paradigm has taken place.

Motor learning

Adaptation of the amplitude (gain) and/or timing (phase) of movements following a training paradigm; typical forms of cerebellar motor learning paradigms include adaptation of the vestibulo-ocular reflex and eyeblink conditioning.

Motor consolidation

Preservation of the level of adaptation of the amplitude and/or timing of movements overnight.

Vestibulo-ocular reflex

(VOR). Reflex movement of the eyes elicited by vestibular stimulation, whereby the eyes move in a direction opposite to that of the head to ensure that the retinal image is kept stable; the reflex is under the control of the vestibulocerebellum.

Homosynaptic

Pertaining to the same synapse. Homosynaptic plasticity is a form of synaptic plasticity in which activity of a particular group of synapses results in synaptic plasticity of the same group of synapses; it can be induced at a single-synapse level.

Heterosynaptic

Pertaining to a different synapse. Heterosynaptic plasticity is a form of synaptic plasticity in which activity of a particular group of synapses results in synaptic plasticity of another group of synapses of the same neuron.

Vestibulocerebellum

The part of the cerebellum that receives direct or indirect vestibular input and controls eye and body reflexes following vestibular input.

Granule cell network

Circuitry consisting of granule cells and interneurons (that is, unipolar brush cells and Golgi cells), which share common mossy fibre inputs and/or are connected through parallel fibres.

Diversity spreading

Expansion of signal coding in the spatial and temporal domain; the granule cell network in the cerebellar cortex is well designed to mediate this process.

Feedforward inhibition

When external inputs excite both a principal neuron and an inhibitory interneuron that inhibits the principal neuron. This phenomenon sharpens the time window during which the principal neuron can fire.

Feedback inhibition

When a principal neuron activates downstream interneurons that inhibit the principal neuron, thereby regulating the subsequent activity of the principal neuron.

First-spike delay

The time interval between the onset of an excitatory input and the generation of the first action potential in a neuron; this interval depends, in part, on the intrinsic excitability of the neuron.

Type 1 phase

Positive rate modulation of the mossy fibres when the vestibular stimulus moves in the ipsilateral direction.

Type 2 phase

Negative rate modulation of the mossy fibres when the vestibular stimulus moves in the ipsilateral direction.

Motor coordination

A combination of motor performance, motor learning and motor consolidation.

Optokinetic reflex

Reflex movement of the eyes in response to visual input, whereby the eyes follow the direction of moving objects to stabilize the retinal image.

Bidirectional plasticity

A form of plasticity that can show both depression and potentiation, depending on the presence or absence of a guiding signal; various sites in the Purkinje cell network show bidirectional plasticity guided by the climbing fibres.

Purkinje cell network

Circuitry consisting of Purkinje cells and molecular layer interneurons, which share common parallel fibre and/or (extra)synaptic climbing fibre inputs.

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Gao, Z., van Beugen, B. & De Zeeuw, C. Distributed synergistic plasticity and cerebellar learning. Nat Rev Neurosci 13, 619–635 (2012). https://doi.org/10.1038/nrn3312

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