microRNA Deficiency in VIP+ Interneurons Leads to Cortical Circuit Dysfunction

VIP+ 中间神经元中的 microRNA 缺乏导致皮质回路功能障碍

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作者:Fang Qiu, Xingfeng Mao, Penglai Liu, Jinyun Wu, Yuan Zhang, Daijing Sun, Yueyan Zhu, Ling Gong, Mengmeng Shao, Keyang Fan, Junjie Chen, Jiangteng Lu, Yan Jiang, Yubin Zhang, Giulia Curia, Anan Li, Miao He

Abstract

Genetically distinct GABAergic interneuron subtypes play diverse roles in cortical circuits. Previous studies revealed that microRNAs (miRNAs) are differentially expressed in cortical interneuron subtypes, and are essential for the normal migration, maturation, and survival of medial ganglionic eminence-derived interneuron subtypes. How miRNAs function in vasoactive intestinal peptide expressing (VIP+) interneurons derived from the caudal ganglionic eminence remains elusive. Here, we conditionally removed Dicer in postmitotic VIP+ interneurons to block miRNA biogenesis. We found that the intrinsic and synaptic properties of VIP+ interneurons and pyramidal neurons were concordantly affected prior to a progressive loss of VIP+ interneurons. In vivo recording further revealed elevated cortical local field potential power. Mutant mice had a shorter life span but exhibited better spatial working memory and motor coordination. Our results demonstrate that miRNAs are indispensable for the function and survival of VIP+ interneurons, and highlight a key role of VIP+ interneurons in cortical circuits.

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