Incomplete vesicular docking limits synaptic strength under high release probability conditions

Elife. 2020 Mar 31;9:e52137. doi: 10.7554/eLife.52137.

Abstract

Central mammalian synapses release synaptic vesicles in dedicated structures called docking/release sites. It has been assumed that when voltage-dependent calcium entry is sufficiently large, synaptic output attains a maximum value of one synaptic vesicle per action potential and per site. Here we use deconvolution to count synaptic vesicle output at single sites (mean site number per synapse: 3.6). When increasing calcium entry with tetraethylammonium in 1.5 mM external calcium concentration, we find that synaptic output saturates at 0.22 vesicle per site, not at 1 vesicle per site. Fitting the results with current models of calcium-dependent exocytosis indicates that the 0.22 vesicle limit reflects the probability of docking sites to be occupied by synaptic vesicles at rest, as only docked vesicles can be released. With 3 mM external calcium, the maximum output per site increases to 0.47, indicating an increase in docking site occupancy as a function of external calcium concentration.

Keywords: calcium concentration; neuroscience; rat; release site; synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Calcium / metabolism*
  • Exocytosis
  • Probability
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / physiology*
  • Tetraethylammonium

Substances

  • Tetraethylammonium
  • Calcium