BK Channels Control Cerebellar Purkinje and Golgi Cell Rhythmicity In Vivo

Guy Cheron,Matthias Sausbier,Bernard Dan,Peter Ruth,Laurent Servais,Ulrike Sausbier,Winfried Neuhuber,Yuan Luo

doi:10.1371/journal.pone.0007991

Abstract

Calcium signaling plays a central role in normal CNS functioning and dysfunction. As cerebellar Purkinje cells express the major regulatory elements of calcium control and represent the sole integrative output of the cerebellar cortex, changes in neural activity- and calcium-mediated membrane properties of these cells are expected to provide important insights into both intrinsic and network physiology of the cerebellum. We studied the electrophysiological behavior of Purkinje cells in genetically engineered alert mice that do not express BK calcium-activated potassium channels and in wild-type mice with pharmacological BK inactivation. We confirmed BK expression in Purkinje cells and also demonstrated it in Golgi cells. We demonstrated that either genetic or pharmacological BK inactivation leads to ataxia and to the emergence of a beta oscillatory field potential in the cerebellar cortex. This oscillation is correlated with enhanced rhythmicity and synchronicity of both Purkinje and Golgi cells. We hypothesize that the temporal coding modification of the spike firing of both Purkinje and Golgi cells leads to the pharmacologically or genetically induced ataxia.

Highlights

Since Purkinje cells (PCs) are solely responsible for the output of the cerebellar cortex, regulation of their firing is central for motor coordination
We found that PC activity was only mildly decreased in BK2/2 mice relative to WT, but that their cerebellum presented a beta rhythm local field potential oscillation phase-locked with ultrarhythmic Purkinje and Golgi cells
PCs recorded in BK2/2 were much more rhythmic than those recorded in WT mice, they were more irregular, as demonstrated by an increased coefficient of variation (CV) (Fig. 2F)

Summary

Introduction

Since Purkinje cells (PCs) are solely responsible for the output of the cerebellar cortex, regulation of their firing is central for motor coordination. PCs spontaneously fire simple spikes in tonic, bursting, or silent modes both in vivo and in vitro This intrinsic excitability is driven by resurgent Na+ channels [1], voltage-gated Ca2+ channels, and Ca2+-activated K+ channels [2,3]. In vitro BK channel blockade leads to a slight simple spike firing rate increase if applied during tonic firing [2,7] and to a complex modification of burst pattern if applied during bursting period [3,7,8] This suggests that BK channels are critical for the fine regulation of Purkinje cells’ intrinsic excitability

Methods

Results

Conclusion