Rapid State-Dependent Alteration in K v 3 Channel Availability Drives Flexible Synaptic Signaling Dependent on Somatic Subthreshold Depolarization

Cell Rep. 2017 Feb 21;18(8):2018-2029. doi: 10.1016/j.celrep.2017.01.068.

Abstract

In many neurons, subthreshold depolarization in the soma can transiently increase action-potential (AP)-evoked neurotransmission via analog-to-digital facilitation. The mechanisms underlying this form of short-term synaptic plasticity are unclear, in part, due to the relative inaccessibility of the axon to direct physiological interrogation. Using voltage imaging and patch-clamp recording from presynaptic boutons of cerebellar stellate interneurons, we observed that depolarizing somatic potentials readily spread into the axon, resulting in AP broadening, increased spike-evoked Ca2+ entry, and enhanced neurotransmission strength. Kv3 channels, which drive AP repolarization, rapidly inactivated upon incorporation of Kv3.4 subunits. This leads to fast susceptibility to depolarization-induced spike broadening and analog facilitation independent of Ca2+-dependent protein kinase C signaling. The spread of depolarization into the axon was attenuated by hyperpolarization-activated currents (Ih currents) in the maturing cerebellum, precluding analog facilitation. These results suggest that analog-to-digital facilitation is tempered by development or experience in stellate cells.

Keywords: Bouton; HCN; Kv3.4; analog signaling; axon; short-term plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axons / metabolism
  • Axons / physiology
  • Calcium / metabolism
  • Cerebellum / metabolism
  • Cerebellum / physiology
  • Interneurons / metabolism
  • Interneurons / physiology
  • Mice
  • Neurons / metabolism
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Potassium Channels / metabolism
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / physiology
  • Protein Kinase C / metabolism
  • Shaw Potassium Channels / metabolism*
  • Signal Transduction / physiology*
  • Synapses / metabolism*
  • Synapses / physiology*
  • Synaptic Transmission / physiology

Substances

  • Kcnc4 protein, mouse
  • Potassium Channels
  • Shaw Potassium Channels
  • Protein Kinase C
  • Calcium