急性应激后的普遍恐惧是由神经元共递质特性的变化引起的

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2024-03-15 DOI:https://www.science.org/doi/10.1126/science.adj5996

Hui-quan Li, Wuji Jiang, Li Ling, Marta Pratelli, Cong Chen, Vaidehi Gupta, Swetha K. Godavarthi, Nicholas C. Spitzer

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引用次数: 0

摘要

将恐惧过度泛化到无害环境是急性应激导致的焦虑症的核心特征，然而人们对恐惧泛化的机制却知之甚少。在这项研究中，我们发现小鼠的泛化恐惧是由于背侧剑突外侧翼的血清素能神经元中的递质从谷氨酸转换为γ-氨基丁酸（GABA）所致。在创伤后应激障碍（PTSD）患者死后的大脑中也发现了类似的递质特性变化。覆盖小鼠的递质开关可防止获得广泛恐惧。皮质酮的释放和糖皮质激素受体的激活介导了这一转换，而及时的抗抑郁治疗阻断了共递质转换和泛化恐惧。我们的研究结果为了解恐惧泛化的机制提供了重要启示。

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Generalized fear after acute stress is caused by change in neuronal cotransmitter identity

Overgeneralization of fear to harmless situations is a core feature of anxiety disorders resulting from acute stress, yet the mechanisms by which fear becomes generalized are poorly understood. In this study, we show that generalized fear in mice results from a transmitter switch from glutamate to γ-aminobutyric acid (GABA) in serotonergic neurons of the lateral wings of the dorsal raphe. Similar change in transmitter identity was found in the postmortem brains of individuals with posttraumatic stress disorder (PTSD). Overriding the transmitter switch in mice prevented the acquisition of generalized fear. Corticosterone release and activation of glucocorticoid receptors mediated the switch, and prompt antidepressant treatment blocked the cotransmitter switch and generalized fear. Our results provide important insight into the mechanisms involved in fear generalization.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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