Department of Psychology, Yale University, New Haven, Connecticut 06520, USA.
Learn Mem. 2013 Jan 17;20(2):109-19. doi: 10.1101/lm.029157.112.
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.
染色质结构的改变被广泛认为与记忆和认知有关，特别是在使用海马依赖的记忆范式方面，包括物体识别、空间记忆和情景恐惧记忆。然而，关于染色质修饰酶在杏仁核依赖的记忆形成中的作用，人们知之甚少。在这里，我们使用生化、行为和神经生理学方法的组合，系统地研究了 p300/CBP 组蛋白乙酰转移酶（HAT）活性在听觉巴甫洛夫恐惧记忆的巩固和再巩固中的作用。我们发现，在恐惧条件反射或恐惧记忆检索后不久，局部注射 c646（一种选择性的 p300/CBP 活性药理学抑制剂）会损害杏仁核外侧核（LA）中与训练和检索相关的组蛋白乙酰化的调节。此外，我们还发现，LA 内注射 c646 会显著损害 LA 中的恐惧记忆巩固、再巩固和相关的神经可塑性。我们的研究结果表明，p300/CBP HAT 活性对杏仁核依赖的巴甫洛夫恐惧记忆的巩固和再巩固至关重要。
