Neuronal activity controls transsynaptic geometry

Sci Rep. 2016 Mar 8:6:22703. doi: 10.1038/srep22703.


The neuronal synapse is comprised of several distinct zones, including presynaptic vesicle zone (SVZ), active zone (AZ) and postsynaptic density (PSD). While correct relative positioning of these zones is believed to be essential for synaptic function, the mechanisms controlling their mutual localization remain unexplored. Here, we employ high-throughput quantitative confocal imaging, super-resolution and electron microscopy to visualize organization of synaptic subdomains in hippocampal neurons. Silencing of neuronal activity leads to reversible reorganization of the synaptic geometry, resulting in a increased overlap between immunostained AZ and PSD markers; in contrast, the SVZ-AZ spatial coupling is decreased. Bayesian blinking and bleaching (3B) reconstruction reveals that the distance between the AZ-PSD distance is decreased by 30 nm, while electron microscopy shows that the width of the synaptic cleft is decreased by 1.1 nm. Our findings show that multiple aspects of synaptic geometry are dynamically controlled by neuronal activity and suggest mutual repositioning of synaptic components as a potential novel mechanism contributing to the homeostatic forms of synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Embryo, Mammalian
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Hippocampus / ultrastructure
  • Microscopy, Confocal
  • Microscopy, Electron
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Rats
  • Synapses / physiology
  • Synapses / ultrastructure*
  • Synaptic Transmission / physiology*
  • Tetrodotoxin / pharmacology
  • Voltage-Gated Sodium Channel Blockers / pharmacology
  • Voltage-Gated Sodium Channels / drug effects
  • Voltage-Gated Sodium Channels / physiology


  • Bsn protein, rat
  • Nerve Tissue Proteins
  • Voltage-Gated Sodium Channel Blockers
  • Voltage-Gated Sodium Channels
  • Tetrodotoxin