iScience (Jun 2020)
AUTS2 Regulation of Synapses for Proper Synaptic Inputs and Social Communication
- 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
Affiliations
- Kei Hori
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan; Corresponding author
- Kunihiko Yamashiro
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Taku Nagai
- Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan
- Wei Shan
- Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan
- Saki F. Egusa
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Kazumi Shimaoka
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Hiroshi Kuniishi
- Department of Neuropsychopharmacology, National Institute of Mental Health, NCNP, Tokyo, 187-8502, Japan; Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, Tokyo, 187-8502, Japan
- Masayuki Sekiguchi
- Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, Tokyo, 187-8502, Japan
- Yasuhiro Go
- Cognitive Genomics Research Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8585, Japan; Department of Physiological Sciences, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan
- Shoji Tatsumoto
- Cognitive Genomics Research Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan
- Mitsuyo Yamada
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan; Department of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan
- Reika Shiraishi
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Kouta Kanno
- Department of Humanities, Faculty of Law, Economics and the Humanities, Kagoshima University, Kagoshima 890-0065, Japan
- Satoshi Miyashita
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Asami Sakamoto
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Manabu Abe
- Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Nigata 951-8585, Japan
- Kenji Sakimura
- Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Nigata 951-8585, Japan
- Masaki Sone
- Department of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan
- Kazuhiro Sohya
- Department of Mental Disorder Research, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Hiroshi Kunugi
- Department of Mental Disorder Research, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan
- Keiji Wada
- Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, Tokyo, 187-8502, Japan
- Mitsuhiko Yamada
- Department of Neuropsychopharmacology, National Institute of Mental Health, NCNP, Tokyo, 187-8502, Japan
- Kiyofumi Yamada
- Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan
- Mikio Hoshino
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo 187-8502, Japan; Corresponding author
- Journal volume & issue
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Vol. 23,
no. 6
p. 101183
Abstract
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.
