The influence of synaptic size on AMPA receptor activation: a Monte Carlo model

PLoS One. 2015 Jun 24;10(6):e0130924. doi: 10.1371/journal.pone.0130924. eCollection 2015.

Abstract

Physiological and electron microscope studies have shown that synapses are functionally and morphologically heterogeneous and that variations in size of synaptic junctions are related to characteristics such as release probability and density of postsynaptic AMPA receptors. The present article focuses on how these morphological variations impact synaptic transmission. We based our study on Monte Carlo computational simulations of simplified model synapses whose morphological features have been extracted from hundreds of actual synaptic junctions reconstructed by three-dimensional electron microscopy. We have examined the effects that parameters such as synaptic size or density of AMPA receptors have on the number of receptors that open after release of a single synaptic vesicle. Our results indicate that the maximum number of receptors that will open after the release of a single synaptic vesicle may show a ten-fold variation in the whole population of synapses. When individual synapses are considered, there is also a stochastical variability that is maximal in small synapses with low numbers of receptors. The number of postsynaptic receptors and the size of the synaptic junction are the most influential parameters, while the packing density of receptors or the concentration of extrasynaptic transporters have little or no influence on the opening of AMPA receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Humans
  • Imaging, Three-Dimensional
  • Microscopy, Electron
  • Monte Carlo Method
  • Probability
  • Receptors, AMPA / metabolism*
  • Regression Analysis
  • Signal Transduction
  • Synapses / metabolism*
  • Synaptic Transmission
  • Synaptic Vesicles / metabolism*

Substances

  • Receptors, AMPA

Grant support

This work was supported by Spanish Ministry of Economy and Competitiveness (NAVAN project and BFU2012-34963, http://www.mineco.gob.es/ (JM JMP JDF)); Centro de Investigación Biomédica en Red (CIBERNED) (CB06/05/0066, http://ciberned.es/ (JDF)); Cajal Blue Brain Project, Spanish partner of the Blue Brain Project initiative from EPFL (http://cajalbbp.cesvima.upm.es/ (JM)); and the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 604102, Human Brain Project (JMP JDF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.