Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage.
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.
Wood
Marcelo A
MA
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. marcelow@sas.upenn.edu
Kaplan
Michael P
MP
Park
Alice
A
Blanchard
Edward J
EJ
Oliveira
Ana M M
AM
Lombardi
Thomas L
TL
Abel
Ted
T
D000818:Animals; D050882:CREB-Binding Protein; D003071:Cognition / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D003463:Cues; D004298:Dopamine / Q000378:metabolism; D004924:Escape Reaction / Q000502:physiology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments; D013569:Synapses / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D010446:Peptide Fragments; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D004298:Dopamine