title: p300/CBP histone acetyltransferase activity is required for newly acquired and reactivated fear memories in the lateral amygdala.
abstract: Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation. Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically examine the role of p300/CBP histone acetyltransferase (HAT) activity in the consolidation and reconsolidation of auditory Pavlovian fear memories. We show that local infusions of c646, a selective pharmacological inhibitor of p300/CBP activity, shortly following either fear conditioning or fear memory retrieval impair training and retrieval-related regulation of histone acetylation in the lateral nucleus of the amygdala (LA). Furthermore, we show that intra-LA infusion of c646 significantly impairs fear memory consolidation, reconsolidation, and associated neural plasticity in the LA. Our findings collectively suggest that p300/CBP HAT activity is critical for the consolidation and reconsolidation of amygdala-dependent Pavlovian fear memories.
authors: Department of Psychology, Yale University, New Haven, Connecticut 06520, USA.
authors: Stephanie A
authors: SA
authors: Maddox
authors: Casey S
authors: CS
authors: Watts
authors: Glenn E
authors: GE
authors: Schafe
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004567:Electrodes, Implanted; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D005239:Fear; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D004791:Enzyme Inhibitors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor