AUTS2 Regulation of Synapses for Proper Synaptic Inputs and Social Communication

• Main Authors: Kei Hori, Kunihiko Yamashiro, Taku Nagai, Wei Shan, Saki F. Egusa, Kazumi Shimaoka, Hiroshi Kuniishi, Masayuki Sekiguchi, Yasuhiro Go, Shoji Tatsumoto, Mitsuyo Yamada, Reika Shiraishi, Kouta Kanno, Satoshi Miyashita, Asami Sakamoto, Manabu Abe, Kenji Sakimura, Masaki Sone, Kazuhiro Sohya, Hiroshi Kunugi, Keiji Wada, Mitsuhiko Yamada, Kiyofumi Yamada, Mikio Hoshino
• Format: Article
• Language: English
• Published: Elsevier 2020-06-01
• Series: iScience
• Subjects: Neuroscience; Behavioral Neuroscience; Molecular Neuroscience; Transcriptomics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004220303680

Summary: 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 the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant 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 with AUTS2 mutations.