Desynchronization of multivesicular release enhances Purkinje cell output

Neuron. 2011 Jun 9;70(5):991-1004. doi: 10.1016/j.neuron.2011.03.029.


The release of neurotransmitter-filled vesicles after action potentials occurs with discrete time courses: submillisecond phasic release that can be desynchronized by activity followed by "delayed release" that persists for tens of milliseconds. Delayed release has a well-established role in synaptic integration, but it is not clear whether desynchronization of phasic release has physiological consequences. At the climbing fiber to Purkinje cell synapse, the synchronous fusion of multiple vesicles is critical for generating complex spikes. Here we show that stimulation at physiological frequencies drives the temporal dispersion of vesicles undergoing multivesicular release, resulting in a slowing of the EPSC on the millisecond timescale. Remarkably, these changes in EPSC kinetics robustly alter the Purkinje cell complex spike in a manner that promotes axonal propagation of individual spikelets. Thus, desynchronization of multivesicular release enhances the precise and efficient information transfer by complex spikes.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Aspartic Acid / pharmacology
  • Biophysical Phenomena / physiology*
  • Calcium / metabolism
  • Cerebellum / cytology*
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / metabolism
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology
  • Linear Models
  • Mice
  • Nerve Fibers / physiology
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Patch-Clamp Techniques / methods
  • Purkinje Cells / drug effects
  • Purkinje Cells / metabolism*
  • Quinoxalines / pharmacology
  • Strontium / pharmacology
  • Synapses / metabolism
  • Time Factors


  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • benzyloxyaspartate
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Aspartic Acid
  • Glutamic Acid
  • Kynurenic Acid
  • Calcium
  • Strontium