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  • Review Article
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Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits

Key Points

  • A widely held assumption is that the same neural computation is performed throughout a uniform circuitry in the adult mammalian cerebellar cortex, and differences in function can be explained primarily by distinct patterns of input and output connectivity.

  • Anatomical, genetic and physiological evidence suggests, however, that the cerebellar cortex is not uniform. Regional differences include variations in cell type, morphology and expression of various molecular markers, most notably zebrin II expression by Purkinje cells.

  • Purkinje cells are considered to be key players within the cerebellar cortex because they provide the sole signal output from the cortex to the cerebellar nuclei. Differences related to zebrin II expression include variations in intrinsic and synaptic physiology and patterns of activity of simple spikes and complex spikes.

  • Mouse mutant models also show that Purkinje cell death occurs in restricted patterns that are related to both motor and potentially non-motor dysfunction.

  • Variations in gene expression and related anatomical and physiological differences therefore result in an assembly of non-uniform cerebellar cortical microcircuits that have different information processing capabilities.

Abstract

The adult mammalian cerebellar cortex is generally assumed to have a uniform cytoarchitecture. Differences in cerebellar function are thought to arise primarily through distinct patterns of input and output connectivity rather than as a result of variations in cortical microcircuitry. However, evidence from anatomical, physiological and genetic studies is increasingly challenging this orthodoxy, and there are now various lines of evidence indicating that the cerebellar cortex is not uniform. Here, we develop the hypothesis that regional differences in properties of cerebellar cortical microcircuits lead to important differences in information processing.

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Figure 1: Classical view of cerebellar cytoarchitecture.
Figure 2: Anatomical location determines the morphology of cerebellar Purkinje cells.
Figure 3: Patterned molecular marker expression in the cerebellar cortex.
Figure 4: Patterned electrophysiological activity in the cerebellar cortex.
Figure 5: The non-uniform nature of cerebellar cortical cytoarchitecture and physiology.

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Acknowledgements

We thank the UK Medical Research Council (N.L.C. & R.A.), Action Medical Research (N.L.C. & R.A), National Science Foundation (E.J.L.), National Institutes of Health (grant 1U54HD083092-01, R.V.S.) and the Bachmann–Strauss Dystonia and Parkinson Foundation (1R01NS089664-01, R.V.S.) for their financial support.

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Adaptive Filter Model (PDF 79 kb)

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Glossary

Long-term depression

A long-lasting decrease in the response of neurons to stimulation of their afferents following a brief patterned stimulus (for example, a 1 Hz stimulus).

Rate coding

A form of neural representation in which the frequency or rate of action potentials over a given time period carries the relevant information. Any information possibly encoded in the temporal structure of the spike train is ignored.

Spike rate modulation

Changes in the frequency or rate of action potentials that are thought to encode information.

Temporal coding

A form of neuronal representation in which the timing of action potentials carries the relevant information. The time of action potentials can be referenced with respect to other action potentials of the same cell or those of other cells.

Chaperone

A protein that mediates the folding or assembly of another polypeptide, but does not form part of the completed structure or participate in its biological function.

One-map hypothesis

The topography of the cerebellar cortex has been defined by different patterns of climbing fibre input, mossy fibre input and Purkinje cell phenotype. Based on embryological development, the one-map hypothesis proposes that the basic units of each map align in the adult animal to form one unitary map.

Optogenetics

A series of recently developed tools that make use of light-activated proteins. Most frequently, light-sensitive ion channels and membrane pumps are used to control the firing rate of neurons, but increasingly other types of proteins are placed under similar light control.

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Cerminara, N., Lang, E., Sillitoe, R. et al. Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits. Nat Rev Neurosci 16, 79–93 (2015). https://doi.org/10.1038/nrn3886

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