Activity-Dependent Gating of Calcium Spikes by A-type K+ Channels Controls Climbing Fiber Signaling in Purkinje Cell Dendrites

Yo Otsu,Païkan Marcaggi,Anne Feltz,Philippe Isope,Mihaly Kollo,Zoltan Nusser,Benjamin Mathieu,Masanobu Kano,Mika Tsujita,Kenji Sakimura,Stéphane Dieudonné

doi:10.1016/j.neuron.2014.08.035

Abstract

SummaryIn cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules.

Highlights

Interactions between synaptic inputs, dendritic excitability, and dendritic morphology give rise to local and global calcium signaling in dendrites (Higley and Sabatini, 2008; Larkum et al, 1999; Sjostrom et al, 2008)
climbing fiber (CF) stimulations evoke widespread calcium transients in Purkinje cell dendrites (Sullivan et al, 2005; Tank et al, 1988), which have been attributed to propagating dendritic calcium spikes
While regenerative events have been recorded from proximal smooth dendrites both in vivo (Fujita, 1968; Kitamura and Hausser, 2011) and in vitro (Davie et al, 2008; Llinas and Sugimori, 1980), the variability of CF calcium transients measured in distal spiny branchlets suggests that calcium spikes may not always occur at distal sites

Summary

Introduction

Interactions between synaptic inputs, dendritic excitability, and dendritic morphology give rise to local and global calcium signaling in dendrites (Higley and Sabatini, 2008; Larkum et al, 1999; Sjostrom et al, 2008). The amplitude of the CF calcium signal is modulated by the somatic holding potential (Wang et al, 2000; Kitamura and Hausser, 2011), by dendritic field depolarization (Midtgaard et al, 1993), by synaptic inhibition of the dendrites (Callaway et al, 1995; Kitamura and Hausser, 2011), and by the activity of PFs (Brenowitz and Regehr, 2005; Wang et al, 2000).

Results

Discussion

Conclusion