Mechanism for long-term memory formation when synaptic strengthening is impaired
Mechanism for long-term memory formation when synaptic strengthening is impaired
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DOI：
10.1073/pnas.1109680108
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发表时间：
2011-11-08
影响因子：
11.1
通讯作者：
Giese, K. Peter
中科院分区：
文献类型：
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作者：
Radwanska, Kasia;Medvedev, Nikolay I.;Giese, K. Peter
长期记忆（LTM）的形成与现有突触的功能强化和其他过程（包括从头突触发生）有关。然而，目前尚不清楚突触发生是否有助于LTM的形成。在这里，使用α-钙/钙调蛋白激酶II自磷酸化缺陷（T286 A）突变体，我们证明，当功能强化严重受损，上下文LTM形成与训练诱导的PSD 95上调，然后持续生成多神经支配的棘，一种突触，其特征是由几个突触前终端接触相同的突触后棘。T286 A突变体中的PSD 95上调和背景LTM形成都需要雷帕霉素哺乳动物靶标（mTOR）的信号传导。此外，我们表明，上下文LTM抵制不稳定的T286 A突变体，表明LTM是不太灵活的突触强化受损时。两者合计，我们认为，激活mTOR信号转导，随后过表达的PSD 95蛋白和突触，有助于形成不变的LTM时，功能增强受损。
Long-term memory (LTM) formation has been linked with functional strengthening of existing synapses and other processes including de novo synaptogenesis. However, it is unclear whether synaptogenesis can contribute to LTM formation. Here, using alpha-calcium/calmodulin kinase II autophosphorylation-deficient (T286A) mutants, we demonstrate that when functional strengthening is severely impaired, contextual LTM formation is linked with training-induced PSD95 up-regulation followed by persistent generation of multiinnervated spines, a type of synapse that is characterized by several presynaptic terminals contacting the same postsynaptic spine. Both PSD95 up-regulation and contextual LTM formation in T286A mutants required signaling by the mammalian target of rapamycin (mTOR). Furthermore, we show that contextual LTM resists destabilization in T286A mutants, indicating that LTM is less flexible when synaptic strengthening is impaired. Taken together, we suggest that activation of mTOR signaling, followed by overexpression of PSD95 protein and synaptogenesis, contributes to formation of invariant LTM when functional strengthening is impaired.