Institute of Physiological Chemistry, Philipps-University Marburg, Marburg, Germany.
Behavioural Neuroscience, Experimental and Biological Psychology, Philipps-University Marburg, Marburg, Germany.
EMBO Rep. 2019 Feb;20(2). doi: 10.15252/embr.201846429. Epub 2018 Dec 14.
Aberrant synaptic function is thought to underlie social deficits in neurodevelopmental disorders such as autism and schizophrenia. Although microRNAs have been shown to regulate synapse development and plasticity, their potential involvement in the control of social behaviour in mammals remains unexplored. Here, we show that deletion of the placental mammal-specific miR379-410 cluster in mice leads to hypersocial behaviour, which is accompanied by increased excitatory synaptic transmission, and exaggerated expression of ionotropic glutamate receptor complexes in the hippocampus. Bioinformatic analyses further allowed us to identify five "hub" microRNAs whose deletion accounts largely for the upregulation of excitatory synaptic genes observed, including Cnih2, Dlgap3, Prr7 and Src. Thus, the miR379-410 cluster acts a natural brake for sociability, and interfering with specific members of this cluster could represent a therapeutic strategy for the treatment of social deficits in neurodevelopmental disorders.
异常的突触功能被认为是神经发育障碍（如自闭症和精神分裂症）中社交缺陷的基础。虽然已经表明 microRNAs 可以调节突触的发育和可塑性，但它们在控制哺乳动物的社交行为方面的潜在作用仍未被探索。在这里，我们表明，删除小鼠中胎盘哺乳动物特异性 miR379-410 簇会导致过度社交行为，这伴随着兴奋性突触传递的增加，以及海马体中离子型谷氨酸受体复合物的过度表达。生物信息学分析进一步使我们能够识别出五个“枢纽” microRNAs，它们的缺失在很大程度上解释了观察到的兴奋性突触基因的上调，包括 Cnih2、Dlgap3、Prr7 和 Src。因此，miR379-410 簇是社交性的天然刹车，干扰该簇的特定成员可能代表治疗神经发育障碍中社交缺陷的一种治疗策略。
