Activity-dependent gating of calcium spikes by A-type K+ channels controls climbing fiber signaling in Purkinje cell dendrites

Neuron. 2014 Oct 1;84(1):137-151. doi: 10.1016/j.neuron.2014.08.035. Epub 2014 Sep 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Calcium Signaling / physiology*
  • Dendrites / physiology*
  • Dendrites / ultrastructure
  • Ion Channel Gating / physiology
  • Kv Channel-Interacting Proteins / physiology*
  • Mice
  • Organ Culture Techniques
  • Purkinje Cells / physiology*
  • Purkinje Cells / ultrastructure
  • Rats
  • Rats, Wistar
  • Signal Transduction / physiology*

Substances

  • Kv Channel-Interacting Proteins