A theory of synaptic transmission

  1. Bin Wang  Is a corresponding author
  2. Olga K Dudko  Is a corresponding author
  1. University of California, San Diego, United States

Abstract

Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters within just milliseconds of the action potential. Yet neurotransmitter release lacks a theoretical framework that is both phenomenologically accurate and mechanistically realistic. Here, we present an analytic theory of the action-potential-triggered neurotransmitter release at the chemical synapse. The theory is demonstrated to be in detailed quantitative agreement with existing data on a wide variety of synapses from electrophysiological recordings in vivo and fluorescence experiments in vitro. Despite up to ten orders of magnitude of variation in the release rates among the synapses, the theory reveals that synaptic transmission obeys a simple, universal scaling law, which we confirm through a collapse of the data from strikingly diverse synapses onto a single master curve. This universality is complemented by the ability of the theory to readily extract, through a fit to the data, the kinetic and energetic parameters that uniquely identify each synapse. The theory provides a means to detect cooperativity among the SNARE complexes that mediate vesicle fusion and reveals such cooperativity in several existing data sets. The theory is further applied to establish connections between molecular constituents of synapses and synaptic function. The theory allows competing hypotheses of short-term plasticity to be tested and identifies the regimes where particular mechanisms of synaptic facilitation dominate or, conversely, fail to account for the existing data for the paired-pulse ratio. The derived trade-off relation between the transmission rate and fidelity shows how transmission failure can be controlled by changing the microscopic properties of the vesicle pool and SNARE complexes. The established condition for the maximal synaptic efficacy reveals that no fine tuning is needed for certain synapses to maintain near-optimal transmission. We discuss the limitations of the theory and propose possible routes to extend it. These results provide a quantitative basis for the notion that the molecular-level properties of synapses are crucial determinants of the computational and information-processing functions in synaptic transmission.

Data availability

The current manuscript is a theoretical study, so no data have been generated for this manuscript. Modelling code is provided in Appendix.

Article and author information

Author details

  1. Bin Wang

    Department of Physics, University of California, San Diego, La Jolla, United States
    For correspondence
    biwang@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3390-8210
  2. Olga K Dudko

    Department of Physics, University of California, San Diego, La Jolla, United States
    For correspondence
    dudko@physics.ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8944-8538

Funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Timothy E Behrens, University of Oxford, United Kingdom

Version history

  1. Received: January 31, 2021
  2. Accepted: October 22, 2021
  3. Accepted Manuscript published: December 31, 2021 (version 1)
  4. Accepted Manuscript updated: January 10, 2022 (version 2)
  5. Version of Record published: January 18, 2022 (version 3)

Copyright

© 2021, Wang & Dudko

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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  1. Bin Wang
  2. Olga K Dudko
(2021)
A theory of synaptic transmission
eLife 10:e73585.
https://doi.org/10.7554/eLife.73585

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https://doi.org/10.7554/eLife.73585

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