AUTS2 regulation of synapses for proper synaptic inputs and social communication
AUTS2 regulation of synapses for proper synaptic inputs and social communication
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AUTS2 调节突触以实现适当的突触输入和社交交流
DOI：
10.1101/871012
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Yamad
中科院分区：
文献类型：
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作者：
Hori Kei;Yamashiro Kunihiko;Nagai Taku;Shan Wei;Egusa Saki F.;Shimaoka Kazumi;Go Yasuhiro;Tatsumoto Shoji;Yamada Mitsuyo;Shiraishi Reika;Kanno Kouta;Miyashita Satoshi;Sakamoto Asami;Abe Manabu;Sakimura Kenji;Sone Masaki;Sohya Kazuhiro;Kunugi Hiroshi;Yamad
突触发育的损伤被认为是导致许多精神疾病的原因。自闭症易感性候选基因2（AUTS2）与自闭症、智力障碍等多种精神疾病有关。尽管AUTS2在神经元迁移和神经发生中的作用已被报道，但其在突触调节中的作用仍不清楚。在这项研究中，我们发现兴奋性突触在auts2缺失的原代培养神经元和auts2突变的前脑中特异性增加。电生理记录和免疫染色显示，在auts2突变的大脑中，兴奋性突触输入和c-fos表达增加，表明兴奋性和抑制性输入平衡的改变增强了大脑的兴奋性。auts2突变小鼠表现出类似自闭症的行为，包括社交障碍和声音交流改变。总之，这些发现表明，AUTS2调节兴奋性突触数量以协调大脑中的E/I平衡，其损害可能是AUTS2突变个体精神疾病病理的基础。
Impairments in synapse development are thought to cause numerous psychiatric disorders.Autism susceptibility candidate 2(AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in theAuts2-deficient primary cultured neurons as well asAuts2mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression inAuts2mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability.Auts2mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals withAUTS2mutations.