Independent regulation of basal neurotransmitter release efficacy by variable Ca²+ influx and bouton size at small central synapses

PLoS Biol. 2012;10(9):e1001396. doi: 10.1371/journal.pbio.1001396. Epub 2012 Sep 25.


The efficacy of action potential evoked neurotransmitter release varies widely even among synapses supplied by the same axon, and the number of release-ready vesicles at each synapse is a major determinant of this heterogeneity. Here we identify a second, equally important, mechanism for release heterogeneity at small hippocampal synapses, the inter-synaptic variation of the exocytosis probability of release-ready vesicles. Using concurrent measurements of vesicular pool sizes, vesicular exocytosis rates, and presynaptic Ca²⁺ dynamics, in the same small hippocampal boutons, we show that the average fusion probability of release-ready vesicles varies among synapses supplied by the same axon with the size of the spike-evoked Ca²⁺ concentration transient. We further show that synapses with a high vesicular release probability exhibit a lower Ca²⁺ cooperativity, arguing that this is a direct consequence of increased Ca²⁺ influx at the active zone. We conclude that variability of neurotransmitter release under basal conditions at small central synapses is accounted for not only by the number of release-ready vesicles, but also by their fusion probabilities, which are set independently of bouton size by variable spike-evoked presynaptic Ca²⁺ influx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Axons / metabolism
  • Buffers
  • Calcium / metabolism*
  • Calcium Signaling*
  • Exocytosis
  • Fluorescence
  • Neurotransmitter Agents / metabolism*
  • Presynaptic Terminals / metabolism*
  • Rats
  • Synapses / metabolism*
  • Synaptic Vesicles / metabolism


  • Buffers
  • Neurotransmitter Agents
  • Calcium