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

Marcelo A Wood; Michael P Kaplan; Alice Park; Edward J Blanchard; Ana M M Oliveira; Thomas L Lombardi; Ted Abel

doi:10.1101/lm.86605

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

Journal article

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

Marcelo A Wood, Michael P Kaplan, Alice Park, Edward J Blanchard, Ana M M Oliveira, Thomas L Lombardi and Ted Abel

Learning & memory (Cold Spring Harbor, N.Y.), Vol.12(2), pp.111-119

03/2005

DOI: 10.1101/lm.86605

PMCID: PMC1074328

PMID: 15805310

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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 CaMKII alpha 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.

Cues

Peptide Fragments

Maze Learning - physiology

Synapses - physiology

CREB-Binding Protein

Mice, Inbred C57BL

Mice, Transgenic

Nuclear Proteins - metabolism

Long-Term Potentiation - genetics

Fear - physiology

Conditioning, Classical - physiology

Escape Reaction - physiology

Hippocampus - metabolism

Animals

Neuronal Plasticity - physiology

Trans-Activators - genetics

Cognition - physiology

Long-Term Potentiation - physiology

Trans-Activators - metabolism

Mice

In Vitro Techniques

Nuclear Proteins - genetics

Dopamine - metabolism

Memory - physiology

Details

Title: Subtitle: Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage
Creators: Marcelo A Wood - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. marcelow@sas.upenn.edu
Michael P Kaplan
Alice Park
Edward J Blanchard
Ana M M Oliveira
Thomas L Lombardi
Ted Abel
Resource Type: Journal article
Publication Details: Learning & memory (Cold Spring Harbor, N.Y.), Vol.12(2), pp.111-119
Publisher: United States
DOI: 10.1101/lm.86605
PMID: 15805310
PMCID: PMC1074328
ISSN: 1072-0502
eISSN: 1549-5485
Language: English
Date published: 03/2005
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065831402771

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