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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Keywords cellular heterogeneity, cerebellar function, mouse, neuroscience, Purkinje cell, spiking activity, TRPC3, zebrin/aldolase C
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Journal eLife
Wu, B. (Bin), Blot, F.G. (François Gc), Wong, A.B. (Aaron Benson), Osório, C. (Catarina), Adolfs, Y, Pasterkamp, R.J, … Schonewille, M. (2019). TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells. eLife, 8. doi:10.7554/eLife.45590