β-Adducin Is Required for Stable Assembly of New Synapses and Improved Memory upon Environmental Enrichment
β-Adducin Is Required for Stable Assembly of New Synapses and Improved Memory upon Environmental Enrichment
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DOI：
10.1016/j.neuron.2011.02.034
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发表时间：
2011-03-24
期刊：
影响因子：
16.2
通讯作者：
Caroni, Pico
中科院分区：
文献类型：
--
作者：
Bednarek, Ewa;Caroni, Pico
学习与新突触的组装相关，但人们对突触发生过程在记忆中的作用知之甚少。在这里，我们发现缺乏β-内收蛋白的小鼠在可塑性增强时无法组装新的突触，并且在环境丰富时表现出长期海马记忆减弱。富集增强了突触动态亚群的拆卸和组装。富集后，新突触的稳定组装取决于 β-内收蛋白的存在，分解涉及通过 PKC 进行的 β-内收蛋白磷酸化，两者都是增强学习所必需的。在没有β-内收蛋白的情况下，富集仍然会导致棘结构的增加，但这些棘上突触的组装受到损害。病毒介导的β-内收蛋白在β-内收蛋白(-/-)小鼠海马颗粒细胞中的重新表达在富集时挽救了新的突触组装和学习。我们的结果提供的证据表明，突触拆卸和新突触的建立对于环境丰富时增强长期学习和记忆都至关重要。
Learning is correlated with the assembly of new synapses, but the roles of synaptogenesis processes in memory are poorly understood. Here, we show that mice lacking beta-Adducin fail to assemble new synapses upon enhanced plasticity and exhibit diminished long-term hippocampal memory upon environmental enrichment. Enrichment-enhanced the disassembly and assembly of dynamic subpopulations of synapses. Upon enrichment, stable assembly of new synapses depended on the presence of beta-Adducin, disassembly involved beta-Adducin phosphorylation through PKC, and both were required for augmented learning. In the absence of beta-Adducin, enrichment still led to an increase in spine structures, but the assembly of synapses at those spines was compromised. Virus-mediated re-expression of beta-Adducin in hippocampal granule cells of beta-Adducin(-/-) mice rescued new synapse assembly and learning upon enrichment. Our results provide evidence that synapse disassembly and the establishment of new synapses are both critically important for augmented long-term learning and memory upon environmental enrichment.