eLife (Sep 2019)

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

  • 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

DOI
https://doi.org/10.7554/eLife.45590
Journal volume & issue
Vol. 8

Abstract

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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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