情景恐惧记忆的巩固、再巩固和消除依赖于蓝斑核中的新蛋白质合成。
Consolidation, reconsolidation, and extinction of contextual fear memory depend on de novo protein synthesis in the locus coeruleus.
机构信息
:Department of Applied Biological Chemistry, Graduate school of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan; Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
:Department of Applied Biological Chemistry, Graduate school of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
出版信息
Brain Res Bull. 2023 Oct 1;202:110746. doi: 10.1016/j.brainresbull.2023.110746. Epub 2023 Aug 19.
Memory consolidation is the process underlying the stabilization of labile short-term memory and the generation of long-term memory for persistent memory storage. The retrieval of contextual fear memory induces two distinct and opposite memory processes: reconsolidation and extinction. Reconsolidation re-stabilizes retrieved memory for re-storage, whereas memory extinction weakens fear memory and generates a new inhibitory memory. Importantly, the requirement for new gene expression is a critical biochemical feature of the consolidation, reconsolidation, and long-term extinction of memory. The locus coeruleus (LC) is a small nucleus in the brain stem that is composed predominantly of noradrenergic neurons that project to many brain regions. Recent studies have shown that the LC plays modulatory roles in the consolidation and extinction of auditory fear memory through its projections to brain regions contributing to memory storage. Here, we show that the LC is required for the consolidation, reconsolidation, and long-term extinction of contextual fear memory. We first observed that c-fos expression was induced in the LC following contextual fear conditioning to induce consolidation and following short and long re-exposure to the conditioning context to induce reconsolidation and long-term extinction, respectively. More importantly, inhibition of protein synthesis in the LC by a micro-infusion of anisomycin blocked the consolidation, reconsolidation, and long-term extinction of contextual fear memory. Our findings suggest that consolidation, reconsolidation, and long-term extinction occur in the LC and that the LC plays an essential role in memory storage and maintenance.
记忆巩固是不稳定的短期记忆稳定化和持久记忆存储产生长时记忆的过程。情境恐惧记忆的提取诱导了两种截然不同的相反记忆过程:再巩固和遗忘。再巩固重新稳定了可重新存储的已检索记忆,而记忆遗忘则削弱了恐惧记忆并产生了新的抑制性记忆。重要的是,新基因表达的要求是记忆巩固、再巩固和长期遗忘的关键生化特征。蓝斑核(LC)是脑干中的一个小核,主要由去甲肾上腺素能神经元组成,这些神经元投射到许多脑区。最近的研究表明,LC 通过其投射到参与记忆存储的脑区,在听觉恐惧记忆的巩固和遗忘中发挥调节作用。在这里,我们表明 LC 是情境恐惧记忆巩固、再巩固和长期遗忘所必需的。我们首先观察到,在进行情境恐惧条件反射以诱导巩固、以及在短暂和长时间重新暴露于条件反射环境以诱导再巩固和长期遗忘后,LC 中的 c-fos 表达被诱导。更重要的是,通过微注射anisomycin 抑制 LC 中的蛋白质合成,阻断了情境恐惧记忆的巩固、再巩固和长期遗忘。我们的发现表明,巩固、再巩固和长期遗忘发生在 LC 中,LC 在记忆存储和维持中起着至关重要的作用。