NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model

Guangjian Qi, Pei Zhang, Tongxia Li, Ming Li, Qian Zhang, Feng He, Lijun Zhang, Hongwei Cai, Xinyuan Lv, Haifa Qiao, Xiaoqian Chen, Jie Ming () and Bo Tian ()
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Guangjian Qi: Huazhong University of Science and Technology
Pei Zhang: Huazhong University of Science and Technology
Tongxia Li: Huazhong University of Science and Technology
Ming Li: Huazhong University of Science and Technology
Qian Zhang: Huazhong University of Science and Technology
Feng He: Huazhong University of Science and Technology
Lijun Zhang: Huazhong University of Science and Technology
Hongwei Cai: Huazhong University of Science and Technology
Xinyuan Lv: Huazhong University of Science and Technology
Haifa Qiao: Shaanxi University of Chinese Medicine
Xiaoqian Chen: Huazhong University of Science and Technology
Jie Ming: Union Hospital, Huazhong University of Science and Technology
Bo Tian: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Emotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior.

Date: 2022
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DOI: 10.1038/s41467-022-28190-2

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