Incomplete vesicular docking limits synaptic strength under high release probability conditions
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.
Data availability
Igor files of the analysis, that contain the entire list of analysis operations are provided as Source Data 1.
Article and author information
Author details
Funding
H2020 European Research Council (294509)
- Gerardo Malagon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany
Version history
- Received: September 23, 2019
- Accepted: March 23, 2020
- Accepted Manuscript published: March 31, 2020 (version 1)
- Version of Record published: April 6, 2020 (version 2)
Copyright
© 2020, Malagon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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