To survive in a dynamic environment, animals need to identify and appropriately respond to stimuli that signal danger 1 . Survival also depends on suppressing the threat-response during a stimulus that predicts the absence of threat (safety) 2 – 5 . An understanding of the biological substrates of emotional memories during a task in which animals learn to flexibly execute defensive responses to a threat-predictive cue and a safety cue is critical for developing treatments for memory disorders such as post-traumatic stress disorder 5 . The centrolateral amygdala is an important node in the neuronal circuit that mediates defensive responses 6 – 9 , and a key brain area for processing and storing threat memories. Here we applied intersectional chemogenetic strategies to inhibitory neurons in the centrolateral amygdala of mice to block cell-type-specific translation programs that are sensitive to depletion of eukaryotic initiation factor 4E (eIF4E) and phosphorylation of eukaryotic initiation factor 2α (p-eIF2α). We show that de novo translation in somatostatin-expressing inhibitory neurons in the centrolateral amygdala is necessary for the long-term storage of conditioned-threat responses, whereas de novo translation in protein kinase Cδ-expressing inhibitory neurons in the centrolateral amygdala is necessary for the inhibition of a conditioned response to a safety cue. Our results provide insight into the role of de novo protein synthesis in distinct inhibitory neuron populations in the centrolateral amygdala during the consolidation of long-term memories. Protein synthesis is required in distinct populations of inhibitory neurons in the mouse amygdala to store memories of danger and safety.

中文翻译：

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杏仁核抑制神经元作为情绪记忆翻译位点

为了在动态环境中生存，动物需要识别危险信号的刺激并做出适当的反应 1 。生存还取决于在预测不存在威胁​​（安全）的刺激期间抑制威胁反应 2 – 5 。在动物学习灵活地对威胁预测线索和安全线索执行防御反应的任务中，了解情感记忆的生物基础对于开发治疗记忆障碍（例如创伤后应激障碍）的方法至关重要 5 。中央外侧杏仁核是介导防御反应的神经回路中的重要节点 6 – 9 ，也是处理和存储威胁记忆的关键大脑区域。在这里，我们将交叉化学遗传学策略应用于小鼠中央外侧杏仁核的抑制性神经元，以阻断对真核起始因子 4E (eIF4E) 耗竭和真核起始因子 2α (p-eIF2α) 磷酸化敏感的细胞类型特异性翻译程序。我们发现，中央外侧杏仁核中表达生长抑素的抑制性神经元的从头翻译对于条件威胁反应的长期储存是必要的，而中央外侧杏仁核中表达蛋白激酶Cδ的抑制性神经元的从头翻译是长期储存条件威胁反应所必需的。抑制对安全提示的条件反应。我们的结果深入了解了长期记忆巩固过程中杏仁核中央外侧不同抑制性神经元群中蛋白质从头合成的作用。小鼠杏仁核中不同的抑制性神经元群需要蛋白质合成来存储危险和安全的记忆。