Coordinated excitatory and inhibitory circuits governing unpredictable threat-induced anxiety
Shuai-Wen Teng,
Xin-Rong Wang,
Zhong-Xiao Yao,
Tianhan He,
Ming-Yuan Gao,
Ying-Ying Che,
Xin-Yue Wei,
Xiao-Lin Chen,
Chao Liu,
Zhe-Yu Chen
Affiliations
Shuai-Wen Teng
Research Center for Basic Medical Sciences, Qilu Hospital of Shandong University, No.107 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China; Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
Xin-Rong Wang
Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
Zhong-Xiao Yao
Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
Tianhan He
Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, China
Ming-Yuan Gao
Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
Ying-Ying Che
Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
Xin-Yue Wei
Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
Xiao-Lin Chen
Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
Chao Liu
Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, China
Zhe-Yu Chen
Research Center for Basic Medical Sciences, Qilu Hospital of Shandong University, No.107 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China; Department of Anatomy and Neurobiology, Shandong Key Laboratory of Mental Disorders and Intelligent Control, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China; Corresponding author
Summary: Anxiety is elicited by excessive apprehension about unpredictable threats. However, the neural circuit governing unpredictable threat induced anxiety remains unclear. Here, we found ventral bed nucleus of the stria terminalis (vBNST) GABAergic neurons displayed selective activation to unpredictable threats through coordinated excitatory input from insular cortex glutamergic neurons and inhibitory input from the lateral nucleus of the amygdala (CeL) somatostatin neurons. Using activity-dependent neuronal tagging technology, we found that unpredictable threat responsive cells in vBNST drive freezing and anxiety via projections to ventral lateral periaqueductal gray (vlPAG) and median nucleus of the amygdala, respectively. Finally, we identified that potassium voltage-gated channel subfamily Q member 3 (KCNQ3) plays an essential role in hyperactivity of vBNST GABAergic neurons induced anxiety. These data revealed a forward inhibitory circuit that determines the selective activation of vBNST in unpredictable threat and anxiety, and suggest that the KCNQ3 channel is a promising target for the treatment of anxiety disorders after unpredictable stress.
