Abstract：
Social deficits are frequently observed in patients suffering from neurodevelopmental disorders, but the molecular mechanisms regulating sociability are still poorly understood. We recently reported that the loss of the microRNA (miRNA) cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. Here, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to larger dendritic spines, increased excitatory synaptic transmission, and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, is sufficient to reinstate normal sociability in miR-379-410 knockout mice. Several actomyosin genes and miR-379-410 family members are reciprocally dysregulated in isogenic human induced pluripotent stem cell (iPSC)-derived neurons harboring a deletion present in patients with Williams-Beuren syndrome, characterized by hypersocial behavior. Together, our results show an miRNA-actomyosin pathway involved in social behavior regulation.
摘要：
在患有神经发育障碍的患者中经常观察到社会缺陷，但是调节社交能力的分子机制仍然知之甚少。我们最近报道了microRNA（miRNA）簇miR-379-410的丢失导致小鼠的超社会行为和焦虑。这里,我们表明，在出生后小鼠海马区的兴奋性神经元中消除miR-379-410可以提高社交能力，但不是焦虑。在细胞层面,miR-379-410在兴奋性神经元中的丢失导致较大的树突棘，兴奋性突触传递增加，以及肌动球蛋白基因网络的上调。三个簇miRNA的再表达，以及肌动球蛋白激活剂ROCK的药理抑制作用，足以恢复miR-379-410敲除小鼠的正常社交能力。几个肌动球蛋白基因和miR-379-410家族成员在等基因人类诱导多能干细胞（iPSC）衍生的神经元中相互失调，这些神经元在Williams-Beuren综合征患者中存在缺失，以超社会行为为特征。一起,我们的结果表明miRNA-肌动球蛋白通路参与社会行为调控。
