TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
- Erasmus Medical Center, Netherlands
- University Medical Center Utrecht, Netherlands
- Technische Universität München, Germany
- University of Oxford, United Kingdom
Abstract
Despite the canonical homogeneous character of its organization, the cerebellum plays differential computational roles in distinct sensorimotor behaviors. Previously we showed that Purkinje cell 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+ Purkinje cells. In addition, TRPC3 regulates complex spike rate and their interaction with simple spikes, exclusively in Z- Purkinje cells. 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 Purkinje cells, conjuring functional heterogeneity in cerebellar sensorimotor integration.
Data availability
All electrophysiology and behavioral data are included in the manuscript and supporting files. Source data files have been provided for Figures 2 to 7 and Figures S4 to S8.
Article and author information
Author details
R Jeroen Pasterkamp
Martijn Schonewille
Funding
European Commission (ERC-Stg #680235)
- Martijn Schonewille
China Scholarship Council (#201306230130)
- Bin Wu
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALW / Zon-Mw)
- Chris I De Zeeuw
European Commission (ERC-Adv)
- Chris I De Zeeuw
European Commission (ERC-POC)
- Chris I De Zeeuw
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jennifer L Raymond, Stanford School of Medicine, United States
Ethics
Animal experimentation: This study was performed under and all of the animals were handled according to a project license approved by the Dutch Central Committee for Animal Experiments (CCD, AVD #101002015273). Each experiment was separately verified and approved by the Animal Welfare Body (IvD/AWB, various numbers). All surgery was performed under isoflurane anesthesia combined with local anesthetics and analgesics in an effort to minimize suffering.
Version history
- Received: February 8, 2019
- Accepted: August 18, 2019
- Accepted Manuscript published: September 5, 2019 (version 1)
- Version of Record published: September 9, 2019 (version 2)
Copyright
© 2019, Wu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
eLife 8:e45590.
https://doi.org/10.7554/eLife.45590
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