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.
The giant proximal CF input controls Ca 2+ plasticity at distal PF-Purkinje synapses
We find mGluR1 activity and Purkinje cell depolarization to control CF calcium influx
Distal CF signaling is mediated by centrifugal dendritic calcium spikes bursts
Dendritic low-threshold A-type K+ channels modulation underlie calcium spike gating
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.