Structural and molecular remodeling of dendritic spine substructures during long-term potentiation

Neuron. 2014 Apr 16;82(2):444-59. doi: 10.1016/j.neuron.2014.03.021.


Synapses store information by long-lasting modifications of their structure and molecular composition, but the precise chronology of these changes has not been studied at single-synapse resolution in real time. Here we describe the spatiotemporal reorganization of postsynaptic substructures during long-term potentiation (LTP) at individual dendritic spines. Proteins translocated to the spine in four distinct patterns through three sequential phases. In the initial phase, the actin cytoskeleton was rapidly remodeled while active cofilin was massively transported to the spine. In the stabilization phase, cofilin formed a stable complex with F-actin, was persistently retained at the spine, and consolidated spine expansion. In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until a late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Dendritic Spines / physiology*
  • Dendritic Spines / ultrastructure
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology*
  • Humans
  • Long-Term Potentiation / physiology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Models, Biological
  • Nerve Tissue Proteins / metabolism
  • Neurons / ultrastructure*
  • Organ Culture Techniques
  • Post-Synaptic Density / metabolism
  • Post-Synaptic Density / ultrastructure
  • Rats
  • Receptors, Neurotransmitter / metabolism
  • Synapses / genetics
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Transduction, Genetic


  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Receptors, Neurotransmitter
  • Glutamic Acid