Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory
Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory
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DOI：
10.1002/hipo.20879
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发表时间：
2012-02-01
期刊：
影响因子：
3.5
通讯作者：
Thomas, Kerrie L.
中科院分区：
文献类型：
--
作者：
Barnes, Philip;Kirtley, Anne;Thomas, Kerrie L.
长期记忆的巩固和再巩固是否依赖于不同性质的分子和细胞过程是有争议的。我们使用一种新的实验策略，将靶向脑源性神经营养因子（BDNF）或zif 268的海马内反义寡聚脱氧核苷酸分别与背景恐惧记忆的块巩固或再巩固相结合，并使用Affymetrix微阵列技术，确定了CA 1中调节的非重叠候选基因的全面列表在巩固和再巩固的初始阶段。在随后的验证实验中使用RT-qPCR，我们估计超过80%的候选人反映了在获得或检索上下文恐惧记忆后真正受到调控的基因转录本。统计和过度代表性的生物信息学分析显示，细胞过程和信号传导机制的差异调节巩固和再巩固，特别是那些与促炎细胞因子信号传导。这预示着这两个记忆过程在质量上和数量上都是不同的。这一实验策略得到了进一步验证，因为细胞因子白细胞介素1（IL-1）的调节后，在CA 1的上下文恐惧条件和恐惧记忆检索，我们首次表明，IL-1受体介导的信号在海马是必要的再巩固。(C)2010 Wiley Periodicals，Inc.
Whether the consolidation and reconsolidation long-term memory relies on qualitatively different molecular and cellular processes is controversial. Using a novel experimental strategy of combining intrahippocampal antisense oligodeoxynucleotides targeting BDNF or zif268 to the block consolidation or reconsolidation of contextual fear memory respectively, and Affymetrix microarray technology, we identified a comprehensive list of nonoverlapping candidate genes regulated in CA1 during the initial stages consolidation and reconsolidation. Using RT-qPCR in subsequent validation experiments, we estimated that over 80% of the candidates reflect gene transcripts truly regulated following the acquisition or retrieval of contextual fear memory. Statistical and over-representation bioinformatics analyses revealed that cellular processes and signaling mechanisms were differentially regulated during consolidation and reconsolidation, particularly those associated with pro-inflammatory cytokine signaling. This predicts that the two mnemonic processes are qualitatively as well as quantitatively distinct. This experimental strategy was further validated because the cytokine interleukin 1 (IL-1) was reciprocally regulated in CA1 after contextual fear conditioning and fear memory retrieval, and we showed for the first time that that IL-1 receptor mediated signaling in the hippocampus was necessary for reconsolidation. (C) 2010 Wiley Periodicals, Inc.