Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice

被引：63

作者：

Nakai, Nobuhiro ^{[1
,2
,3
]}

Nagano, Masatoshi ^{[4
]}

Saitow, Fumihito ^{[4
]}

Watanabe, Yasuhito ^{[2
,5
,6
]}

Kawamura, Yoshinobu ^{[2
]}

Kawamoto, Akiko ^{[2
]}

Tamada, Kota ^{[1
,2
]}

Mizuma, Hiroshi ^{[7
]}

Onoe, Hirotaka ^{[7
]}

Watanabe, Yasuyoshi ^{[7
]}

Monai, Hiromu ^{[1
]}

Hirase, Hajime ^{[1
]}

Nakatani, Jin ^{[8
]}

Inagaki, Hirofumi ^{[4
]}

Kawada, Tomoyuki ^{[4
]}

Miyazaki, Taisuke ^{[9
]}

Watanabe, Masahiko ^{[9
]}

Sato, Yuka ^{[10
]}

Okabe, Shigeo ^{[10
]}

Kitamura, Kazuo ^{[10
]}

Kano, Masanobu ^{[10
]}

Hashimoto, Kouichi ^{[2
]}

Suzuki, Hidenori ^{[4
,11
]}

Takumi, Toru ^{[1
,2
,11
]}

机构：

[1] RIKEN Brain Sci Inst, Wako, Saitama 3510198, Japan

[2] Hiroshima Univ, Grad Sch Biomed Sci, Minami Ku, Hiroshima 7348553, Japan

[3] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068501, Japan

[4] Nippon Med Sch, Grad Sch Med, Bunkyo Ku, Tokyo 1138602, Japan

[5] Univ Hosp, Dept Clin Neurobiol, D-69120 Heidelberg, Germany

[6] German Canc Res Ctr, D-69120 Heidelberg, Germany

[7] RIKEN Ctr Life Sci Technol, Chuo Ku, Kobe, Hyogo 6500047, Japan

[8] Shiga Univ Med Sci, Otsu, Shiga 5202192, Japan

[9] Hokkaido Univ, Grad Sch Med, Dept Anat & Embryol, Kita Ku, Sapporo, Hokkaido 0608638, Japan

[10] Univ Tokyo, Grad Sch Med, Bunkyo Ku, Tokyo 1138654, Japan

[11] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol CREST, Tokyo, Japan

来源：

SCIENCE ADVANCES | 2017年 / 3卷 / 06期

关键词：

MOUSE MODEL; SOMATOSENSORY CORTEX; SPECTRUM DISORDERS; BARREL CORTEX; IN-VIVO; PLASTICITY; BRAIN; INHIBITION; DUPLICATION; MODULATION;

D O I：

10.1126/sciadv.1603001

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Serotonin is a critical modulator of cortical function, and its metabolism is defective in autism spectrum disorder (ASD) brain. How serotonin metabolism regulates cortical physiology and contributes to the pathological and behavioral symptoms of ASD remains unknown. We show that normal serotonin levels are essential for the maintenance of neocortical excitation/inhibition balance, correct sensory stimulus tuning, and social behavior. Conversely, low serotonin levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication) result in impairment of the same phenotypes. Restoration of normal serotonin levels in 15q dup mice revealed the reversibility of a subset of ASD-related symptoms in the adult. These findings suggest that serotonin may have therapeutic potential for discrete ASD symptoms.

引用

页数：13

共 45 条

[1] THALAMOCORTICAL RESPONSES OF MOUSE SOMATOSENSORY (BARREL) CORTEX INVITRO [J].