Reconsolidation or Extinction: Transcription Factor Switch in the Determination of Memory Course after Retrieval
Reconsolidation or Extinction: Transcription Factor Switch in the Determination of Memory Course after Retrieval
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DOI：
10.1523/jneurosci.6066-10.2011
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发表时间：
2011-04-13
影响因子：
5.3
通讯作者：
Romano, Arturo
中科院分区：
文献类型：
--
作者：
de la Fuente, Veronica;Freudenthal, Ramiro;Romano, Arturo
在恐惧条件反射中，厌恶性刺激很容易与情境特征相关联。短暂的再暴露于训练环境会导致恐惧记忆重新巩固，而长时间的再暴露会导致记忆消退。海马基因表达调控在背景记忆巩固和再巩固过程中起着关键作用。然而，决定记忆是否会重新巩固或消失的机制尚不清楚。在这里，我们证明了两个进化相关的转录因子在小鼠海马体中的相反作用。我们发现核因子-κ B（NF-κ B）是恐惧记忆再巩固所必需的。相反，钙调磷酸酶抑制NF-κ B B和诱导活化T细胞核因子（NFAT）核转位之间的再巩固和灭绝的过渡。因此，海马抑制钙调磷酸酶和NFAT独立损害记忆消退，而抑制NF-κ B增强记忆消退。这些发现代表了对决定记忆在提取后再加工的分子机制的第一次洞察，支持了将记忆导向重新巩固或消失的转录开关。精确的分子表征postretrieval过程的恐惧记忆障碍的治疗策略的发展具有潜在的重要性。
In fear conditioning, aversive stimuli are readily associated with contextual features. A brief reexposure to the training context causes fear memory reconsolidation, whereas a prolonged reexposure induces memory extinction. The regulation of hippocampal gene expression plays a key role in contextual memory consolidation and reconsolidation. However, the mechanisms that determine whether memory will reconsolidate or extinguish are not known. Here, we demonstrate opposing roles for two evolutionarily related transcription factors in the mouse hippocampus. We found that nuclear factor-kappa B (NF-kappa B) is required for fear memory reconsolidation. Conversely, calcineurin phosphatase inhibited NF-kappa B and induced nuclear factor of activated T-cells (NFAT) nuclear translocation in the transition between reconsolidation and extinction. Accordingly, the hippocampal inhibition of both calcineurin and NFAT independently impaired memory extinction, whereas inhibition of NF-kappa B enhanced memory extinction. These findings represent the first insight into the molecular mechanisms that determine memory reprocessing after retrieval, supporting a transcriptional switch that directs memory toward reconsolidation or extinction. The precise molecular characterization of postretrieval processes has potential importance to the development of therapeutic strategies for fear memory disorders.