Heterosynaptic molecular dynamics: locally induced propagating synaptic accumulation of CaM kinase II

Neuron. 2009 Feb 12;61(3):351-8. doi: 10.1016/j.neuron.2008.12.030.

Abstract

Calcium-calmodulin-dependent protein kinase II (CaMKII) is a key mediator of synaptic plasticity and learning. Global pyramidal cell glutamate stimulation induces translocation of CaMKII from dendritic shafts to spines. Here we show that local dendritic stimulation by puffing glutamate onto a region containing 7-32 synapses induces translocation of CaMKII to synapses initially at the puff site but that translocation subsequently spreads within dendrites to the distal dendrite arbor, resulting in a persistent, widespread synaptic accumulation. This locally induced propagating synaptic (L-IPS) accumulation of CaMKII requires activation of NMDA receptors and L-type Ca(2+) channels and is preceded by a Ca(2+) spike. L-IPS translocation of CaMKII alters biochemical signaling and is associated with an increase in AMPA receptor GluR1 at both stimulated and nonstimulated synapses and thus provides a molecular mechanism for heterosynaptic plasticity.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cells, Cultured
  • Dendrites / enzymology*
  • Dendrites / ultrastructure
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Hippocampus / enzymology*
  • Hippocampus / ultrastructure
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Protein Transport / physiology
  • Rats
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism
  • Receptors, Glutamate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / enzymology*
  • Synapses / ultrastructure
  • Synaptic Potentials / drug effects
  • Synaptic Potentials / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Calcium Channels, L-Type
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • glutamate receptor ionotropic, AMPA 1