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记忆巩固需要快速的神经元翻译
作者:小柯机器人 发布时间:2020/1/23 16:29:20

美国纽约大学Eric Klann、洛克菲勒大学Nathaniel Heintz等研究人员合作利用细胞类型特异性药物诱导的蛋白合成抑制作用,揭示了记忆巩固需要快速的神经元翻译。相关论文2020年1月20日在线发表在《自然—神经科学》上。

研究人员开发了一种结合敲入小鼠和化学遗传(针对细胞类型特异性药物诱导的蛋白质合成抑制)方法,其可实现真核生物起始因子2α的快速和可逆磷酸化,从而导致体内50%的一般翻译受到抑制。研究人员使用细胞类型特异性药物诱导的蛋白合成抑制作用发现,泛神经元和外侧杏仁核(LA)内兴奋性神经元中的靶向蛋白合成抑制损害了长期记忆。这可以通过人工化学激活LA神经元来恢复,尽管需要以刺激的普遍化为代价。相反,在遗传上减少LA兴奋性神经元中的真核生物起始因子2α磷酸化可增强记忆力,但会降低记忆保真度和行为灵活性。这些发现表明,威胁记忆巩固期间需要特定于细胞的翻译程序。

据悉,需要新的蛋白质合成来巩固记忆,但是现有阻止翻译的方法缺乏时空精度和细胞类型特异性,从而无法研究蛋白质合成的细胞特异性作用。

附:英文原文

Title: Cell-type-specific drug-inducible protein synthesis inhibition demonstrates that memory consolidation requires rapid neuronal translation

Author: Prerana Shrestha, Pinar Ayata, Pedro Herrero-Vidal, Francesco Longo, Alexandra Gastone, Joseph E. LeDoux, Nathaniel Heintz, Eric Klann

Issue&Volume: 2020-01-20

Abstract: New protein synthesis is known to be required for the consolidation of memories, yet existing methods of blocking translation lack spatiotemporal precision and cell-type specificity, preventing investigation of cell-specific contributions of protein synthesis. Here we developed a combined knock-in mouse and chemogenetic approach for cell-type-specific drug-inducible protein synthesis inhibition that enables rapid and reversible phosphorylation of eukaryotic initiation factor 2α, leading to inhibition of general translation by 50% in vivo. We use cell-type-specific drug-inducible protein synthesis inhibition to show that targeted protein synthesis inhibition pan-neuronally and in excitatory neurons in the lateral amygdala (LA) impaired long-term memory. This could be recovered with artificial chemogenetic activation of LA neurons, although at the cost of stimulus generalization. Conversely, genetically reducing phosphorylation of eukaryotic initiation factor 2α in excitatory neurons in the LA enhanced memory strength but reduced memory fidelity and behavioral flexibility. Our findings provide evidence for a cell-specific translation program during consolidation of threat memories.

DOI: 10.1038/s41593-019-0568-z

Source: https://www.nature.com/articles/s41593-019-0568-z

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新if:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex