Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage

  1. Marcelo A. Wood1,4,
  2. Michael P. Kaplan1,
  3. Alice Park1,2,
  4. Edward J. Blanchard1,
  5. Ana M.M. Oliveira1,
  6. Thomas L. Lombardi1,3, and
  7. Ted Abel1,4
  1. 1Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

Abstract

Deletions, translocations, or point mutations in the CREB-binding protein (CBP) gene have been associated with Rubinstein-Taybi Syndrome; a human developmental disorder characterized by retarded growth and reduced mental function. To examine the role of CBP in memory, transgenic mice were generated in which the CaMKIIα promoter drives expression of an inhibitory truncated CBP protein in forebrain neurons. Examination of hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to underlie memory storage, revealed significantly reduced late-phase LTP induced by dopamine-regulated potentiation in hippocampal slices from CBP transgenic mice. However, four-train induced late-phase LTP is normal. Behaviorally, CBP transgenic mice exhibited memory deficits in spatial learning in the Morris water maze and deficits in long-term memory for contextual fear conditioning, two hippocampus-dependent tasks. Together, these results demonstrate that CBP is involved in specific forms of hippocampal synaptic plasticity and hippocampus-dependent long-term memory formation.

Footnotes

  • Article and publication are at http://www.learnmem.org/cgi/doi/10.1101/lm.86605.

  • 2 Present address: Department of Cell Biology, Georgetown Univer-Medical Center, Washington, DC 20057, USA

  • 3 Present address: Keck School of Medicine, University of Southern California, Los Angeles 90033, CA, USA

    • Accepted January 4, 2005.
    • Received September 24, 2004.
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