title: Dissociable roles for histone acetyltransferases p300 and PCAF in hippocampus and perirhinal cortex-mediated object memory.
abstract: The importance of histone acetylation for certain types of memory is now well established. However, the specific contributions of the various histone acetyltransferases to distinct memory functions remain to be determined; therefore, we employed selective histone acetyltransferase protein inhibitors and short-interference RNAs to evaluate the roles of CREB-binding protein (CBP), E1A-binding protein (p300) and p300/CBP-associated factor (PCAF) in hippocampus and perirhinal cortex (PRh)-mediated object memory. Rats were tested for short- (STM) and long-term memory (LTM) in the object-in-place task, which relies on the hippocampus and PRh for spatial memory and object identity processing, respectively. Selective inhibition of these histone acetyltransferases by small-interfering RNA and pharmacological inhibitors targeting the HAT domain produced dissociable effects. In the hippocampus, CBP or p300 inhibition impaired long-term but not short-term object memory, while inhibition of PCAF impaired memory at both delays. In PRh, HAT inhibition did not impair STM, and only CBP and PCAF inhibition disrupted LTM; p300 inhibition had no effects. Messenger RNA analyses revealed findings consistent with the pattern of behavioral effects, as all three enzymes were upregulated in the hippocampus (dentate gyrus) following learning, whereas only CBP and PCAF were upregulated in PRh. These results demonstrate, for the first time, the necessity of histone acetyltransferase activity for PRh-mediated object memory and indicate that the specific mnemonic roles of distinctive histone acetyltransferases can be dissociated according to specific brain regions and memory timeframe.
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.|Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Mitchnick
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.|Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
authors.forename: S D
authors.initials: SD
authors.lastname: Creighton
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.|Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Cloke
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Wolter
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Zaika
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Christen
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Van Tiggelen
authors.affiliation: Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.|Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: B E
authors.initials: BE
authors.lastname: Kalisch
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.|Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
authors.forename: B D
authors.initials: BD
authors.lastname: Winters
mesh_terms: D000818:Animals; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D008297:Male; D057567:Memory, Long-Term; D008570:Memory, Short-Term; D000071039:Perirhinal Cortex / Q000378:metabolism* / Q000502:physiology; D020318:Rats, Long-Evans; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D050881:E1A-Associated p300 Protein; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
keywords: Accell siRNA; C646; CBP; embelin; epigenetics; histone acetylation; object recognition; object-in-place; plumbagin; rat