1. Neuroscience
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Cerebellar modules operate at different frequencies

  1. Haibo Zhou
  2. Zhanmin Lin
  3. Kai Voges
  4. Chiheng Ju
  5. Zhenyu Gao
  6. Laurens WJ Bosman
  7. Tom JH Ruigrok
  8. Freek E Hoebeek
  9. Chris I De Zeeuw
  10. Martijn Schonewille  Is a corresponding author
  1. Erasmus MC, Netherlands
  2. Netherlands Institute for Neuroscience, Netherlands
Research Article
  • Cited 139
  • Views 4,413
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Cite this article as: eLife 2014;3:e02536 doi: 10.7554/eLife.02536

Abstract

Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. Here we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depends on activation of TRPC3, and that this property is relevant for all cerebellar functions.

Article and author information

Author details

  1. Haibo Zhou

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  2. Zhanmin Lin

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  3. Kai Voges

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  4. Chiheng Ju

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  5. Zhenyu Gao

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  6. Laurens WJ Bosman

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  7. Tom JH Ruigrok

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  8. Freek E Hoebeek

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  9. Chris I De Zeeuw

    Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  10. Martijn Schonewille

    Erasmus MC, Rotterdam, Netherlands
    For correspondence
    m.schonewille@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: The experiments performed in this study were approved by the local animal ethical committee ("Dier Experimenten Commissie", DEC).

Reviewing Editor

  1. Dora E Angelaki, Baylor College of Medicine, United States

Publication history

  1. Received: February 13, 2014
  2. Accepted: May 3, 2014
  3. Accepted Manuscript published: May 7, 2014 (version 1)
  4. Version of Record published: June 10, 2014 (version 2)

Copyright

© 2014, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

    1. Neuroscience

    TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells

    Bin Wu et al.
    Research Advance Updated

    Despite the canonical homogeneous character of its organization, the cerebellum plays differential computational roles in distinct sensorimotor behaviors. Previously, we showed that Purkinje cell (PC) activity differs between zebrin-negative (Z–) and zebrin-positive (Z+) modules (Zhou et al., 2014). Here, using gain-of-function and loss-of-function mouse models, we show that transient receptor potential cation channel C3 (TRPC3) controls the simple spike activity of Z–, but not Z+ PCs. In addition, TRPC3 regulates complex spike rate and their interaction with simple spikes, exclusively in Z– PCs. At the behavioral level, TRPC3 loss-of-function mice show impaired eyeblink conditioning, which is related to Z– modules, whereas compensatory eye movement adaptation, linked to Z+ modules, is intact. Together, our results indicate that TRPC3 is a major contributor to the cellular heterogeneity that introduces distinct physiological properties in PCs, conjuring functional heterogeneity in cerebellar sensorimotor integration.

    1. Neuroscience

    Neural Circuits: All Purkinje cells are not created equal

    Catarina Albergaria, Megan R Carey
    Insight

    Although the wiring of the cerebellar cortex appears to be uniform, the neurons in this region of the brain behave more differently from each other than previously thought.

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