TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
Wu, Bin; Blot, François Gc; Wong, Aaron Benson; Osório, Catarina; Adolfs, Youri; Pasterkamp, R. Jeroen; Hartmann, Jana; Becker, Esther Be; Boele, Henk Jan; De Zeeuw, Chris I.; Schonewille, Martijn
(2019) eLife, volume 8
(Article)
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 (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
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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.
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Keywords: cellular heterogeneity, cerebellar function, mouse, neuroscience, Purkinje cell, spiking activity, TRPC3, zebrin/aldolase C, General Biochemistry,Genetics and Molecular Biology, General Immunology and Microbiology, General Neuroscience, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2050-084X
Publisher: eLife Sciences Publications
Note: Funding Information: We kindly thank Laura Post for mouse breeding; Nadia Khosravinia for help with behavior experiment; Yarmo Mackenbach for aid with editing the movie; Joshua J White and Dick Jaarsma for discussions and comments on the manuscript. This work was supported by an ERC starter grant (ERC- Stg #680235; MS), China Scholarship Council (#201306230130; BW), the Netherlands Organization for Scientific Research (NWO-ALW; CIDZ), the Dutch Organization for Medical Sciences (ZonMW; CIDZ), ERC-adv and ERC-POC (CIDZ), and the Center for Integrated Protein Science Munich (CIPSM; JH). Funding Information: We kindly thank Laura Post for mouse breeding; Nadia Khosravinia for help with behavior experiment; Yarmo Mackenbach for aid with editing the movie; Joshua J White and Dick Jaarsma for discussions and comments on the manuscript. This work was supported by an ERC starter grant (ERC-Stg #680235; MS), China Scholarship Council (#201306230130; BW), the Netherlands Organization for Scientific Research (NWO-ALW; CIDZ), the Dutch Organization for Medical Sciences (ZonMW; CIDZ), ERC-adv and ERC-POC (CIDZ), and the Center for Integrated Protein Science Munich (CIPSM; JH). Publisher Copyright: © Wu et al.
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