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

TY - JOUR

T1 - TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells

AU - Wu, Bin

AU - Blot, François Gc

AU - Wong, Aaron Benson

AU - Osório, Catarina

AU - Adolfs, Youri

AU - Pasterkamp, R Jeroen

AU - Hartmann, Jana

AU - Becker, Esther Be

AU - Boele, Henk-Jan

AU - De Zeeuw, Chris I

AU - Schonewille, Martijn

N1 - © 2019, Wu et al.

PY - 2019/5/25

Y1 - 2019/5/25

N2 - 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.

AB - 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.

U2 - 10.7554/eLife.45590

DO - 10.7554/eLife.45590

M3 - Article

C2 - 31486767

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

ER -