Synaptic nanomodules underlie the organization and plasticity of spine synapses

Nat Neurosci. 2018 May;21(5):671-682. doi: 10.1038/s41593-018-0138-9. Epub 2018 Apr 23.


Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size. Live-cell time-lapse super-resolution imaging reveals that NMDA receptor-dependent increases in spine size are accompanied both by enhanced mobility of pre- and postsynaptic modules that remain aligned with each other and by a coordinated increase in the number of nanomodules. These findings suggest a simplified model for experience-dependent structural plasticity relying on an unexpectedly modular nanomolecular architecture of synaptic proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Spines / physiology*
  • Dendritic Spines / ultrastructure
  • Disks Large Homolog 4 Protein / genetics
  • Disks Large Homolog 4 Protein / metabolism
  • Immunohistochemistry
  • Long-Term Potentiation / physiology
  • Mice
  • Models, Neurological
  • Neuronal Plasticity / physiology*
  • Plasmids / genetics
  • Primary Cell Culture
  • Rats
  • Receptors, Presynaptic / physiology
  • Synapses / physiology*
  • Synaptic Vesicles / physiology


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Receptors, Presynaptic