Structural basis of long-term potentiation in single dendritic spines

Nature. 2004 Jun 17;429(6993):761-6. doi: 10.1038/nature02617. Epub 2004 Jun 9.


Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling that has been proposed to be a cellular basis of learning and memory. How structural remodelling supports synaptic plasticity, such as long-term potentiation, and whether such plasticity is input-specific at the level of the individual spine has remained unknown. We investigated the structural basis of long-term potentiation using two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons. Here we show that repetitive quantum-like photorelease (uncaging) of glutamate induces a rapid and selective enlargement of stimulated spines that is transient in large mushroom spines but persistent in small spines. Spine enlargement is associated with an increase in AMPA-receptor-mediated currents at the stimulated synapse and is dependent on NMDA receptors, calmodulin and actin polymerization. Long-lasting spine enlargement also requires Ca2+/calmodulin-dependent protein kinase II. Our results thus indicate that spines individually follow Hebb's postulate for learning. They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Calmodulin / metabolism
  • Dendrites / physiology*
  • Electric Conductivity
  • Glutamic Acid / metabolism
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Memory / physiology
  • Neuronal Plasticity / physiology
  • Photolysis
  • Photons
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Actins
  • Calmodulin
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid