Strong evidence has implicated proteasome-mediated protein degradation in the memory consolidation process. However, due to the use of pharmacological approaches, the cell type specificity of this remains unknown. Here, we used neuron-specific and novel astrocyte-specific CRISPR–dCas9–KRAB–MECP2 plasmids to inhibit protein degradation in a cell type-specific manner in the amygdala of male rats. We found that while inhibition of neuronal, but not astrocytic, protein degradation impaired performance during the training session, both resulted in impaired contextual fear memory retention. Together, these data provide the first evidence of a cell type-specific role for protein degradation in the memory consolidation process.

中文翻译：

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神经元和星形胶质细胞蛋白质降解对恐惧记忆的形成至关重要

强有力的证据表明在记忆巩固过程中蛋白酶体介导的蛋白质降解。然而，由于使用药理学方法，其细胞类型特异性仍然未知。在这里，我们使用神经元特异性和新型星形胶质细胞特异性 CRISPR–dCas9–KRAB–MECP2 质粒以细胞类型特异性方式抑制雄性大鼠杏仁核中的蛋白质降解。我们发现，虽然抑制神经元而非星形胶质细胞蛋白质降解会损害训练期间的表现，但两者都会导致情境恐惧记忆保留受损。总之，这些数据提供了记忆巩固过程中蛋白质降解的细胞类型特异性作用的第一个证据。