Abstract
Over the past several decades, theories about cerebellar learning have evolved. A relatively simple view that highlighted the contribution of one major form of heterosynaptic plasticity to cerebellar motor learning has given way to a plethora of perspectives that suggest that many different forms of synaptic and non-synaptic plasticity, acting at various sites, can control multiple types of learning behaviour. However, there still seem to be contradictions between the various hypotheses with regard to the mechanisms underlying cerebellar learning. The challenge is therefore to reconcile these different views and unite them into a single overall concept. Here I review our current understanding of the changes in the activity of cerebellar Purkinje cells in different ‘microzones’ during various forms of learning. I describe an emerging model that indicates that the activity of each microzone is bound to either increase or decrease during the initial stages of learning, depending on the directional and temporal demands of its downstream circuitry and the behaviour involved.
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Acknowledgements
This work is dedicated to J. I. Simpson, former supervisor of the author. The author is funded by the Dutch Organization for Medical Sciences (ZonMw), Life Sciences (ALW-ENW-Klein), the European Research Council (Advanced and Proof of Concept grants), the EU LISTEN Innovative Training Network programme, the Medical NeuroDelta programme, LSH-NWO (Crossover, INTENSE), Albinism Vriendenfonds NIN, van Raamsdonk fonds, and the Trustfonds of Erasmus University, Rotterdam. He is grateful to J. Kruisbrink and S. Wolff who assisted with the bibliography.
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Nature Reviews Neuroscience thanks R. Apps, who co-reviewed with J. Pickford; T. Ebner, who co-reviewed with M. Streng; and G. Hesslow for their contribution to the peer review of this work.
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Glossary
- Control system
-
A system that regulates the behaviour of an animal using control loops.
- Training
-
The process of instructions, rehearsal and feedback that leads to learning.
- Cerebellar learning
-
The induction of a lasting alteration in cerebellar behavior or the potential thereof.
- Microzones
-
Small, sagittally organized networks of cerebellar Purkinje cells and interneurons dedicated to the control of a specific aspect of autonomic, motor or cognitive function.
- Microcomplex
-
A cerebellar cortical microzone of Purkinje cells and an associated small group of cerebellar nucleus cells that are dedicated to the control of a specific aspect of autonomic, motor or cognitive function.
- Micromodules
-
Microcomplexes of Purkinje cells and cerebellar nucleus cells connected with a small cluster of neurons in the inferior olive that together control a specific aspect of autonomic, motor or cognitive function.
- Complex spikes
-
The low-frequency all-or-none spikes of a Purkinje cell that are evoked by activity in its climbing fibre input.
- Simple spikes
-
The high-frequency spikes of a Purkinje cell that are intrinsically generated or evoked by activity in its parallel fibre input.
- Long-term depression
-
(LTD). A process involving postsynaptic changes that renders the synapse less sensitive to an input.
- Long-term potentiation
-
(LTP). A process involving postsynaptic changes that renders the synapse more sensitive to an input.
- Net polarity of neurotransmissions
-
The ultimate excitatory or inhibitory outcome of a set of synapses that connect different neurons in series.
- Excitability
-
The propensity of a neuron to generate, beyond a certain threshold, an output signal (the action potential) from a given input signal.
- Floccular complex
-
The combination of the flocculus and the paraflocculus.
- Vestibulocerebellum
-
The region of the cerebellum that receives prominent inputs from the vestibular apparatus and controls behaviours that depend on the balance of the body in space.
- Unipolar brush cells
-
A class of glutamatergic interneurons found in the granular layer of the cerebellar cortex.
- Magnitude sensitivity
-
The ratio of the amplitude of spike modulation to the amplitude of modulation of the position of a moving part of the body.
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De Zeeuw, C.I. Bidirectional learning in upbound and downbound microzones of the cerebellum. Nat Rev Neurosci 22, 92–110 (2021). https://doi.org/10.1038/s41583-020-00392-x
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DOI: https://doi.org/10.1038/s41583-020-00392-x
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