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
- Cited 5
- Views 1,309
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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.
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.
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.
Reviewing Editor
- Jennifer L Raymond, Stanford School of Medicine, United States
Publication 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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