Sequestration of serum response factor in the hippocampus impairs long-term spatial memory

J Neurochem. 2005 Apr;93(2):269-78. doi: 10.1111/j.1471-4159.2004.03016.x.


The formation of long-term memory has been shown to require protein kinase-mediated gene expression. One such kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), can lead to the phosphorylation of serum response factor (SRF) and Elk-1, enhancing the expression of target genes. However, a direct involvement of these transcription factors in memory storage has not been demonstrated. We have employed an oligonucleotide decoy technique to interrogate SRF and Elk-1. Previously, it has been shown that intra-amygdalal infusion of small double-stranded decoy oligonucleotides for nuclear factor-kappaB (NFkappaB) can impair long-term memory for fear-potentiated startle. Using this approach, we found that intra-hippocampal infusion of NFkappaB decoy oligonucleotides also impairs long-term spatial memory, consistent with a role for this factor in long-term memory storage. Decoy oligonucleotides containing the binding site for SRF, as confirmed by shift-western, did not influence memory acquisition but impaired long-term spatial memory. Analysis of search behavior during the transfer test revealed deficits consistent with a loss of precise platform location information. In contrast, oligonucleotides with a binding site for either Elk-1 or another target of ERK activity, SMAD3/SMAD4, did not interfere with memory formation or storage. These findings suggest that SRF-mediated gene expression is required for long-term spatial memory.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Memory Disorders / metabolism*
  • NF-kappa B / administration & dosage
  • NF-kappa B / metabolism
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Rats
  • Rats, Long-Evans
  • Serum Response Factor / metabolism*
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology*
  • Time Factors


  • NF-kappa B
  • Serum Response Factor