Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory

Ruth M. Barrett, Melissa Malvaez, Eniko Kramar, Dina P. Matheos, Abraham Arrizon, Sara M. Cabrera, Gary Lynch, Robert W. Greene, Marcelo A. Wood

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1545-1556
Number of pages12
JournalNeuropsychopharmacology
Volume36
Issue number8
DOIs
StatePublished - 2011

    Fingerprint

Keywords

  • CBP
  • histone acetylation
  • long-term memory
  • long-term potentiation

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Barrett, R. M., Malvaez, M., Kramar, E., Matheos, D. P., Arrizon, A., Cabrera, S. M., Lynch, G., Greene, R. W., & Wood, M. A. (2011). Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory. Neuropsychopharmacology, 36(8), 1545-1556. https://doi.org/10.1038/npp.2011.61