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p300/CBP-Associated Factor Selectively Regulates the Extinction of Conditioned Fear
- Source :
- The Journal of Neuroscience. 32:11930-11941
- Publication Year :
- 2012
- Publisher :
- Society for Neuroscience, 2012.
-
Abstract
- It is well established that the activity of chromatin-modifying enzymes is crucial for regulating gene expression associated with hippocampal-dependent memories. However, very little is known about how these epigenetic mechanisms influence the formation of cortically dependent memory, particularly when there is competition between opposing memory traces, such as that which occurs during the acquisition and extinction of conditioned fear. Here we demonstrate, in C57BL/6 mice, that the activity of p300/CBP-associated factor (PCAF) within the infralimbic prefrontal cortex is required for long-term potentiation and is necessary for the formation of memory associated with fear extinction, but not for fear acquisition. Further, systemic administration of the PCAF activator SPV106 enhances memory for fear extinction and prevents fear renewal. The selective influence of PCAF on fear extinction is mediated, in part, by a transient recruitment of the repressive transcription factor ATF4 to the promoter of the immediate early genezif268, which competitively inhibits its expression. Thus, within the context of fear extinction, PCAF functions as a transcriptional coactivator, which may facilitate the formation of memory for fear extinction by interfering with reconsolidation of the original memory trace.
- Subjects :
- Male
Article
Extinction, Psychological
Mice
SYNAPTIC PLASTICITY
Conditioning, Psychological
Animals
Humans
p300-CBP Transcription Factors
Prefrontal cortex
DNA METHYLATION
LONG-TERM-MEMORY, MEDIAL PREFRONTAL CORTEX, SYNAPTIC PLASTICITY, TRANSCRIPTION FACTORS, HISTONE ACETYLTRANSFERASE, EPIGENETIC MECHANISMS, BASOLATERAL AMYGDALA, MODIFYING ENZYMES, DNA METHYLATION, TRUNCATED FORM
Communication
MEDIAL PREFRONTAL CORTEX
Long-term memory
business.industry
General Neuroscience
ATF4
Long-term potentiation
Fear
social sciences
BASOLATERAL AMYGDALA
humanities
Mice, Inbred C57BL
TRANSCRIPTION FACTORS
HEK293 Cells
LONG-TERM-MEMORY
EPIGENETIC MECHANISMS
PCAF
Synaptic plasticity
Trans-Activators
MODIFYING ENZYMES
Memory consolidation
HISTONE ACETYLTRANSFERASE
business
Psychology
Neuroscience
Immediate early gene
TRUNCATED FORM
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....5a1fe212941dc5fd7a63d0a7f636e4da