Activity-induced Targeting of Profilin and Stabilization of Dendritic Spine Morphology

Nat Neurosci. 2003 Nov;6(11):1194-200. doi: 10.1038/nn1135. Epub 2003 Oct 12.

Abstract

Morphological changes in dendritic spines have been implicated in connective plasticity in brain circuitry, but the underlying pathway leading from synaptic transmission to structural change is unknown. Using primary neurons expressing GFP-tagged proteins, we found that profilin, a regulator of actin polymerization, is targeted to spine heads when postsynaptic NMDA receptors are activated and that actin-based changes in spine shape are concomitantly blocked. Profilin targeting was triggered by electrical stimulation patterns known to induce the long-term changes in synaptic responsiveness associated with memory formation. These results suggest that, in addition to electrophysiological changes, NMDA receptor activation initiates changes in the actin cytoskeleton of dendritic spines that stabilize synaptic structure.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Bacterial Proteins / metabolism
  • Botulinum Toxins, Type A / pharmacology
  • Calcium / metabolism
  • Cell Count
  • Cells, Cultured
  • Chickens
  • Contractile Proteins*
  • Dendrites / metabolism*
  • Dendrites / physiology
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Luminescent Proteins / metabolism
  • Magnesium / pharmacology
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins / metabolism*
  • Microscopy, Confocal
  • Neuromuscular Agents / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / cytology*
  • Neurons / metabolism
  • Neurons / physiology
  • Potassium Chloride / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Profilins
  • Receptors, Glutamate / classification
  • Receptors, Glutamate / metabolism
  • Time Factors
  • Transfection

Substances

  • Bacterial Proteins
  • Contractile Proteins
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Glial Fibrillary Acidic Protein
  • Luminescent Proteins
  • Microfilament Proteins
  • Neuromuscular Agents
  • Pfn1 protein, mouse
  • Profilins
  • Receptors, Glutamate
  • yellow fluorescent protein, Bacteria
  • Glutamic Acid
  • Potassium Chloride
  • Botulinum Toxins, Type A
  • Magnesium
  • Calcium