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

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)....

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Main Authors: Bin Wu, François GC Blot, Aaron Benson Wong, Catarina Osório, Youri Adolfs, R Jeroen Pasterkamp, Jana Hartmann, Esther BE Becker, Henk-Jan Boele, Chris I De Zeeuw, Martijn Schonewille
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/45590
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author Bin Wu
François GC Blot
Aaron Benson Wong
Catarina Osório
Youri Adolfs
R Jeroen Pasterkamp
Jana Hartmann
Esther BE Becker
Henk-Jan Boele
Chris I De Zeeuw
Martijn Schonewille
author_facet Bin Wu
François GC Blot
Aaron Benson Wong
Catarina Osório
Youri Adolfs
R Jeroen Pasterkamp
Jana Hartmann
Esther BE Becker
Henk-Jan Boele
Chris I De Zeeuw
Martijn Schonewille
author_sort Bin Wu
collection DOAJ
description 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.
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spelling doaj.art-a9026aa4734a4afca2461feffd8a1e972022-12-22T02:03:12ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.45590TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cellsBin Wu0https://orcid.org/0000-0003-4198-1661François GC Blot1Aaron Benson Wong2https://orcid.org/0000-0003-1650-2710Catarina Osório3Youri Adolfs4R Jeroen Pasterkamp5https://orcid.org/0000-0003-1631-6440Jana Hartmann6Esther BE Becker7https://orcid.org/0000-0002-5238-4902Henk-Jan Boele8Chris I De Zeeuw9https://orcid.org/0000-0001-5628-8187Martijn Schonewille10https://orcid.org/0000-0002-2675-1393Department of Neuroscience, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Neuroscience, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Neuroscience, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Neuroscience, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Translational Neuroscience, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment of Translational Neuroscience, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsInstitute of Neuroscience, Technical University Munich, Munich, GermanyDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomDepartment of Neuroscience, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands; Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences, Amsterdam, NetherlandsDepartment of Neuroscience, Erasmus Medical Center, Rotterdam, NetherlandsDespite 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.https://elifesciences.org/articles/45590cerebellar functionPurkinje cellzebrin/aldolase CTRPC3cellular heterogeneityspiking activity
spellingShingle Bin Wu
François GC Blot
Aaron Benson Wong
Catarina Osório
Youri Adolfs
R Jeroen Pasterkamp
Jana Hartmann
Esther BE Becker
Henk-Jan Boele
Chris I De Zeeuw
Martijn Schonewille
TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
eLife
cerebellar function
Purkinje cell
zebrin/aldolase C
TRPC3
cellular heterogeneity
spiking activity
title TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
title_full TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
title_fullStr TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
title_full_unstemmed TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
title_short TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells
title_sort trpc3 is a major contributor to functional heterogeneity of cerebellar purkinje cells
topic cerebellar function
Purkinje cell
zebrin/aldolase C
TRPC3
cellular heterogeneity
spiking activity
url https://elifesciences.org/articles/45590
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