NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model.
NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model.
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NAc-VTA 回路是三腔替代社交失败应激小鼠模型中情绪应激诱发的焦虑样行为的基础
DOI：
10.1038/s41467-022-28190-2
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发表时间：
2022-01-31
影响因子：
16.6
通讯作者：
Tian B
中科院分区：
文献类型：
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作者：
Qi G;Zhang P;Li T;Li M;Zhang Q;He F;Zhang L;Cai H;Lv X;Qiao H;Chen X;Ming J;Tian B
情绪应激被认为是精神疾病的重要致病因素。然而，电路机制在很大程度上仍然不清楚。使用三腔室替代性社会失败应激（3C-VSDS）小鼠模型，我们在这里表明，慢性情绪应激（CES）诱导焦虑样行为和短暂的社会互动的变化。腹侧被盖区（VTA）的多巴胺能神经元需要控制这种行为缺陷。CES诱导的腹侧被盖区多巴胺能神经元过度活跃参与了先天性焦虑环境中的焦虑样行为。腹侧被盖区多巴胺能神经元的化学发生激活直接触发焦虑样行为，而这些神经元的化学发生抑制促进对CES诱导的焦虑样行为的恢复。此外，VTA多巴胺能神经元接收核脑桥（NAc）的投射在CES小鼠被激活。NAc-VTA回路的双向调节模拟或逆转了CES诱导的焦虑样行为。综上所述，我们提出，NAc-VTA电路关键地建立和调节CES诱导的焦虑样行为。这项研究不仅表征了代表CES细微差别的临床前模型，而且还提供了对类似移情行为的回路水平神经元过程的洞察。
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.