Activation of CaMKII in single dendritic spines during long-term potentiation

Nature. 2009 Mar 19;458(7236):299-304. doi: 10.1038/nature07842.


Calcium/calmodulin-dependent kinase II (CaMKII) plays a central part in long-term potentiation (LTP), which underlies some forms of learning and memory. Here we monitored the spatiotemporal dynamics of CaMKII activation in individual dendritic spines during LTP using two-photon fluorescence lifetime imaging microscopy, in combination with two-photon glutamate uncaging. Induction of LTP and associated spine enlargement in single spines triggered transient ( approximately 1 min) CaMKII activation restricted to the stimulated spines. CaMKII in spines was specifically activated by NMDA receptors and L-type voltage-sensitive calcium channels, presumably by nanodomain Ca(2+) near the channels, in response to glutamate uncaging and depolarization, respectively. The high degree of compartmentalization and channel specificity of CaMKII signalling allow stimuli-specific spatiotemporal patterns of CaMKII signalling and may be important for synapse-specificity of synaptic plasticity.

Publication types

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

MeSH terms

  • Animals
  • Calcium / antagonists & inhibitors
  • Calcium / metabolism
  • Calcium Channels, L-Type / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cell Line
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Dendritic Spines / enzymology*
  • Dendritic Spines / physiology*
  • Enzyme Activation / drug effects
  • Fluorescence
  • Fluorescence Resonance Energy Transfer
  • Glutamic Acid / metabolism
  • Hippocampus / cytology
  • Humans
  • Kinetics
  • Long-Term Potentiation / physiology*
  • Photons
  • Rats
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / metabolism
  • Synaptic Potentials / physiology
  • Time Factors


  • Calcium Channels, L-Type
  • Chelating Agents
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium