TRPC3 is essential for functional heterogeneity of cerebellar Purkinje cells

Abstract

Despite the canonical homogenous character of its organization, the cerebellum plays differential computational roles in distinct types of sensorimotor behaviors. However, the molecular and cell physiological underpinnings are unclear. Here we determined the contribution of transient receptor potential cation channel type C3 (TRPC3) to signal processing in different cerebellar modules. Using gain-of-function and loss-of-function mouse models, we found that TRPC3 controls the simple spike activity of zebrin-negative (Z-), but not of zebrin-positive (Z+), Purkinje cells. Moreover, in vivo TRPC3 also regulated complex spike firing and its interaction with simple spikes exclusively in Z- Purkinje cells. Finally, we found that eyeblink conditioning, related to Z- modules, but not compensatory eye movement adaptation, linked to Z+ modules, was affected in TRPC3 loss-of-function mice. Together, our results indicate that TRPC3 is essential for the cellular heterogeneity that introduces distinct physiological properties in an otherwise homogeneous population of Purkinje cells, conjuring functional heterogeneity in cerebellar sensorimotor integration.