Ca(2+)-dependent enhancement of release by subthreshold somatic depolarization

Nat Neurosci. 2011 Jan;14(1):62-8. doi: 10.1038/nn.2718. Epub 2010 Dec 19.


In many neurons, subthreshold somatic depolarization can spread electrotonically into the axon and modulate subsequent spike-evoked transmission. Although release probability is regulated by intracellular Ca(2+), the Ca(2+) dependence of this modulatory mechanism has been debated. Using paired recordings from synaptically connected molecular layer interneurons (MLIs) of the rat cerebellum, we observed Ca(2+)-mediated strengthening of release following brief subthreshold depolarization of the soma. Two-photon microscopy revealed that, at the axon, somatic depolarization evoked Ca(2+) influx through voltage-sensitive Ca(2+) channels and facilitated spike-evoked Ca(2+) entry. Exogenous Ca(2+) buffering diminished these Ca(2+) transients and eliminated the strengthening of release. Axonal Ca(2+) entry elicited by subthreshold somatic depolarization also triggered asynchronous transmission that may deplete vesicle availability and thereby temper release strengthening. In this cerebellar circuit, activity-dependent presynaptic plasticity depends on Ca(2+) elevations resulting from both sub- and suprathreshold electrical activity initiated at the soma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axons / metabolism
  • Axons / physiology
  • Calcium / metabolism
  • Calcium / physiology*
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Cerebellum / physiology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Egtazic Acid
  • EGTA acetoxymethyl ester
  • Calcium