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

Summary

In 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

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  The giant proximal CF input controls Ca ²⁺ plasticity at distal PF-Purkinje synapses

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  We find mGluR1 activity and Purkinje cell depolarization to control CF calcium influx

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  Distal CF signaling is mediated by centrifugal dendritic calcium spikes bursts

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  Dendritic low-threshold A-type K+ channels modulation underlie calcium spike gating

Abstract

Climbing fibers supervise cerebellar learning expressed as calcium-dependent plasticity at the parallel synapses on Purkinje cells. Otsu et al. find that activity-dependent parameters control heterosynaptic climbing fiber signaling by gating calcium spikes in Purkinje cell dendrites.