Besnard Antoine, Laroche Serge, Caboche Jocelyne
INSERM, UMRS 952, Physiopathologie des Maladies du Système Nerveux Central, 9 Quai Saint Bernard, 75005, Paris, France.
Brain Struct Funct. 2014 Jan;219(1):415-30. doi: 10.1007/s00429-013-0505-y. Epub 2013 Feb 7.
Over the past few years multiple studies have attempted to uncover molecular signatures of memory reconsolidation when compared to consolidation. In the present study we used immunocytochemical detection of the MAPK/ERK1/2 pathway, to track activated neuronal circuits in the hippocampus and amygdala recruited during the consolidation and reconsolidation of a contextual fear conditioning (CFC) memory. We report selective differences in magnitude and temporal dynamics of activated ERK1/2 signalling in different subregions of these two structures between the post-training and post-retrieval periods, except in the dentate gyrus, where the patterns of activation were similar. We then focused on this brain area to dissect out the patterns of downstream ERK1/2 signalling components, including the phosphorylation of MSK-1 and histone H3 on ser10, along with the induction of the Immediate Early Genes (IEGs) Arc/Arg3.1, c-Fos and Zif268/Egr1 following CFC training and retrieval. We found that the completion of the nucleosomal response as well as the induction of IEGs shorter during the reconsolidation period as compared to consolidation. Our results shed new light on the cellular mechanisms underlying the consolidation and reconsolidation processes engaged following CFC training and retrieval and further extend the notion that memory reconsolidation is not mechanistically a repetition of consolidation. In addition, we provide evidence that the strength of a previously established CFC memory is characterized by distinct patterns of ERK1/2 activation in different hippocampal and amygdalar subfields upon CFC memory recall. Our results emphasize the differences between consolidation and reconsolidation processes in relation to contextual fear memories.
在过去几年中,多项研究试图揭示与记忆巩固相比,记忆重新巩固的分子特征。在本研究中,我们使用免疫细胞化学检测MAPK/ERK1/2信号通路,以追踪在情境恐惧条件反射(CFC)记忆的巩固和重新巩固过程中,海马体和杏仁核中被激活的神经回路。我们报告了在训练后和检索后期间,这两个结构的不同亚区域中,激活的ERK1/2信号在幅度和时间动态上的选择性差异,但齿状回除外,其激活模式相似。然后,我们聚焦于这个脑区,剖析下游ERK1/2信号成分的模式,包括MSK-1和组蛋白H3在ser10位点的磷酸化,以及CFC训练和检索后立即早期基因(IEGs)Arc/Arg3.1、c-Fos和Zif268/Egr1的诱导。我们发现,与巩固期相比,重新巩固期的核小体反应完成以及IEGs的诱导时间更短。我们的结果为CFC训练和检索后所涉及的巩固和重新巩固过程的细胞机制提供了新的线索,并进一步扩展了记忆重新巩固在机制上不是巩固的重复这一概念。此外,我们提供证据表明,先前建立的CFC记忆的强度,在CFC记忆回忆时,通过不同海马体和杏仁核亚区中ERK1/2激活的不同模式来表征。我们的结果强调了与情境恐惧记忆相关的巩固和重新巩固过程之间的差异。