Spine-type-specific recruitment of newly synthesized AMPA receptors with learning

Science. 2008 Feb 22;319(5866):1104-7. doi: 10.1126/science.1149967.

Abstract

The stabilization of long-term memories requires de novo protein synthesis. How can proteins, synthesized in the soma, act on specific synapses that participate in a given memory? We studied the dynamics of newly synthesized AMPA-type glutamate receptors (AMPARs) induced with learning using transgenic mice expressing the GluR1 subunit fused to green fluorescent protein (GFP-GluR1) under control of the c-fos promoter. We found learning-associated recruitment of newly synthesized GFP-GluR1 selectively to mushroom-type spines in adult hippocampal CA1 neurons 24 hours after fear conditioning. Our results are consistent with a "synaptic tagging" model to allow activated synapses to subsequently capture newly synthesized receptor and also demonstrate a critical functional distinction in the mushroom spines with learning.

Publication types

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

MeSH terms

  • Animals
  • Conditioning, Psychological
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Doxycycline / pharmacology
  • Extinction, Psychological
  • Fear
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Learning / physiology*
  • Long-Term Potentiation
  • Male
  • Memory
  • Mice
  • Mice, Transgenic
  • Protein Transport
  • Pyramidal Cells / metabolism*
  • Pyramidal Cells / ultrastructure
  • Receptors, AMPA / biosynthesis
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Synapses / metabolism*

Substances

  • Receptors, AMPA
  • Recombinant Fusion Proteins
  • Doxycycline
  • glutamate receptor ionotropic, AMPA 1