Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. On the contrary, translin KO mice exhibited deficits in N-methyl-d-aspartate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity.

中文翻译：

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translin/trax RNase 复合物在海马突触可塑性中的选择性作用

活性依赖的局部蛋白质合成对于突触特异性、持久的可塑性至关重要。局部蛋白质合成的异常与精神疾病有关。我们最近已将 translin/trax microRNA 降解酶鉴定为活化突触中蛋白质合成的新型介质。此外，缺乏 translin/trax 的 translin 敲除 (KO) 小鼠表现出在脆性 X 综合征小鼠模型（脆性 X 智力低下蛋白-FMRP-KO 小鼠）中发现的一些行为异常。因此，识别与 translin/trax 相互作用的信号通路以支持持续的突触可塑性是翻译相关的目标。在此，作为实现这一目标的第一步，我们已经评估了 translin/trax 对依赖于不同分子机制的多个海马突触可塑性范式的要求。我们发现缺乏 translin/trax 的小鼠表现出持续海马可塑性形式的选择性损伤，这需要突触后蛋白激酶 A (PKA) 活性。相比之下，依赖于突触前 PKA 的持久形式的可塑性不受影响。此外，这些小鼠没有表现出夸张的代谢型谷氨酸受体介导的长期突触抑制 (mGluR-LTD)，这是 FMRP KO 小鼠的标志。相反，translin KO 小鼠表现出 N-甲基-d-天冬氨酸受体 (NMDAR) 依赖性 LTD 的缺陷，这种表型在 FMRP 敲除中未观察到。综合起来，