Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory
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To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories.
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Disrupted long-term OPP but not NOP memory, along with impaired hippocampal LTP and reduced histone H2B, H3 and H4 acetylation, were found in CREB-binding protein-flox mice microinjected with AAV-Cre into the dorsal hippocampus to produce hippocampal CREB-binding protein depletion.
“Disrupted long-term OPP, but not NOP, memory, along with impaired hippocampal LTP and reduced histone H2B, H3 and H4 acetylation, were found in the CREB-binding protein-flox mice microinjected with AAV-Cre into the dorsal hippocampus to produce hippocampal CREB-binding protein depletion”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Barrett et al., 2011
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- Authors
- Barrett, R. M., Malvaez, M., Kramar, E., Matheos, D. P., Arrizon, A., Cabrera, S. M., Lynch, G., Greene, R. W., & Wood, M. A.
- Affiliations
- University of California, Irvine (US)
- Allergan (United States) (US)
- Dallas VA Medical Center (US)
- Corresponding author
- Wood, Marcelo A
- Venue
- Neuropsychopharmacology
- Published
- 2011-04-20
- Volume
- 36
- Issue
- 8
- Pages
- 1545-1556
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3138668
- OpenAlex
- W1963551704
- Cited by
- 243
- References
- 70
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 22 · 2023: 9 · 2022: 18 · 2021: 14 · 2020: 17 · 2019: 17 · 2018: 6 · 2017: 14 · 2016: 23 · 2015: 9 · 2014: 28 · 2013: 28 · 2012: 14
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Whitehall Foundation
- Multidisciplinary University Research Initiative
- Office of Naval Research
- National Institute of Mental Health (R01MH080297, R01MH081004, F31MH85494, F31MH085494)
- National Institute on Drug Abuse (F31DA293682, F31DA029368)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- CREB-binding protein, histone acetylation, histone modifications, hippocampal CA1, long-term potentiation, long-term memory, memory consolidation, CREB phosphorylation, P300, contextual fear memory, object recognition memory, synaptic plasticity, chromatin modification
- MeSH terms
- Animals, Hippocampus, Histones, Mice, Inbred C57BL, Long-Term Potentiation, Mice, Knockout, CREB-Binding Protein, Mice, Memory, Long-Term
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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