TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells.
Wu B., Blot FGC., Wong AB., Osório C., Adolfs Y., Pasterkamp RJ., Hartmann J., Becker EBE., Boele H-J., De Zeeuw CI., Schonewille M.
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.