Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity

Nat Neurosci. 2004 Oct;7(10):1104-12. doi: 10.1038/nn1311. Epub 2004 Sep 7.

Abstract

The synapse is a highly organized cellular specialization whose structure and composition are reorganized, both positively and negatively, depending on the strength of input signals. The mechanisms orchestrating these changes are not well understood. A plausible locus for the reorganization of synapse components and structure is actin, because it serves as both cytoskeleton and scaffold for synapses and exists in a dynamic equilibrium between F-actin and G-actin that is modulated bidirectionally by cellular signaling. Using a new FRET-based imaging technique to monitor F-actin/G-actin equilibrium, we show here that tetanic stimulation causes a rapid, persistent shift of actin equilibrium toward F-actin in the dendritic spines of rat hippocampal neurons. This enlarges the spines and increases postsynaptic binding capacity. In contrast, prolonged low-frequency stimulation shifts the equilibrium toward G-actin, resulting in a loss of postsynaptic actin and of structure. This bidirectional regulation of actin is actively involved in protein assembly and disassembly and provides a substrate for bidirectional synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Animals
  • Brain / metabolism*
  • Brain / ultrastructure
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Electric Stimulation
  • Fluorescence Resonance Energy Transfer
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Image Cytometry
  • Mice
  • NIH 3T3 Cells
  • Neuronal Plasticity / physiology*
  • Nonlinear Dynamics
  • Organ Culture Techniques
  • Protein Binding
  • Rats
  • Synaptic Membranes / metabolism*
  • Synaptic Transmission / physiology
  • Time Factors
  • Up-Regulation / physiology

Substances

  • Actins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases