Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1
Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1
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DOI：
10.1523/jneurosci.3032-07.2008
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发表时间：
2008-02-13
影响因子：
5.3
通讯作者：
Sheng, Morgan
中科院分区：
文献类型：
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作者：
Hung, Albert Y.;Futai, Kensuke;Sheng, Morgan
树突棘结构的经验依赖性变化可能有助于学习和记忆。突触后骨架蛋白Shank家族由三个基因编码，在中枢兴奋性突触的突触后密度(PSD)中含量丰富。在培养的海马神经元中表达时，Shank可促进树突棘的成熟和扩大。最近，Shank3基因被认为与人类自闭症有关，这表明了Shank蛋白在正常认知发育中的重要作用。在这里，我们报告了Shank1基因敲除小鼠的表型。Shank1突变体表现出PSD蛋白组成改变；树突棘缩小；PSD更小、更薄；基础突触传递更弱。突触可塑性的标准测量是正常的。在行为上，他们与焦虑相关的行为增加，背景恐惧记忆受损。值得注意的是，Shank1基因缺陷的小鼠在空间学习任务中表现出增强的表现；然而，它们在这一任务中的长期记忆保持能力受到了损害。这些结果肯定了Shank1在体内对突触结构和功能的重要性，并突出了Shank1在特定认知过程中的不同作用，这一特征可能与人类自闭症谱系障碍有关。
Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines. Recently, Shank3 has been genetically implicated in human autism, suggesting an important role for Shank proteins in normal cognitive development. Here, we report the phenotype of Shank1 knock-out mice. Shank1 mutants showed altered PSD protein composition; reduced size of dendritic spines; smaller, thinner PSDs; and weaker basal synaptic transmission. Standard measures of synaptic plasticity were normal. Behaviorally, they had increased anxiety-related behavior and impaired contextual fear memory. Remarkably, Shank1-deficient mice displayed enhanced performance in a spatial learning task; however, their long-term memory retention in this task was impaired. These results affirm the importance of Shank1 for synapse structure and function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders.