Cooperative stochastic binding and unbinding explain synaptic size dynamics and statistics

PLoS Comput Biol. 2017 Jul 13;13(7):e1005668. doi: 10.1371/journal.pcbi.1005668. eCollection 2017 Jul.

Abstract

Synapses are dynamic molecular assemblies whose sizes fluctuate significantly over time-scales of hours and days. In the current study, we examined the possibility that the spontaneous microscopic dynamics exhibited by synaptic molecules can explain the macroscopic size fluctuations of individual synapses and the statistical properties of synaptic populations. We present a mesoscopic model, which ties the two levels. Its basic premise is that synaptic size fluctuations reflect cooperative assimilation and removal of molecules at a patch of postsynaptic membrane. The introduction of cooperativity to both assimilation and removal in a stochastic biophysical model of these processes, gives rise to features qualitatively similar to those measured experimentally: nanoclusters of synaptic scaffolds, fluctuations in synaptic sizes, skewed, stable size distributions and their scaling in response to perturbations. Our model thus points to the potentially fundamental role of cooperativity in dictating synaptic remodeling dynamics and offers a conceptual understanding of these dynamics in terms of central microscopic features and processes.

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Computational Biology
  • Models, Neurological
  • Neurons / metabolism*
  • Particle Size
  • Protein Binding
  • Rats
  • Stochastic Processes
  • Synapses / metabolism*
  • Synaptic Transmission / physiology*

Grant support

This work was supported by: Israel Science Foundation Grant No. 1175/14 to NEZ (isf.org.il); Israel Science Foundation Grant No. 1566/11 to NB (isf.org.il); and the Adelis Foundation, to NEZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.