机构：[1]Department of Rehabilitation of Children’s Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310003, China[2]Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain‑machine Integration, State Key Laboratory of Brain‑machine Intelligence, Zhejiang University, Hangzhou 311121, China[3]NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China[4]Innovative Institute of Basic Medical Sciences of Zhejiang University (Yuhang), Hangzhou 310058, China[5]JNU‑HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, China[6]Department of Traditional Chinese Medicine, Xuanwu Hospital of Capital Medical University, Beijing 100053, China首都医科大学宣武医院[7]Pillar of STEM Education, College of Education Sciences, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511453, China
Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of similar to 40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680(+/+)) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680(+/+) mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680(+/+) mice.
基金：
National Natural Science Foundation of China [31970902, U22A20306, 3192010300]; Municipal Administration of Hospitals Incubating Program [PZ2023009]; Key-Area R&D Program of Guangdong Province [2019B030335001]; Autism Research Special Fund of Zhejiang Foundation for Disabled Persons [2022003]
第一作者机构：[1]Department of Rehabilitation of Children’s Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310003, China[2]Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain‑machine Integration, State Key Laboratory of Brain‑machine Intelligence, Zhejiang University, Hangzhou 311121, China[3]NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China
通讯作者：
通讯机构：[1]Department of Rehabilitation of Children’s Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310003, China[2]Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain‑machine Integration, State Key Laboratory of Brain‑machine Intelligence, Zhejiang University, Hangzhou 311121, China[7]Pillar of STEM Education, College of Education Sciences, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511453, China
