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

• 成果类型: Article
• 署名作者: Li, Hui-quan; Jiang, Wuji; Ling, Li; Pratelli, Marta; Chen, Cong; Gupta, Vaidehi; Godavarthi, Swetha K.; Spitzer, Nicholas C.
• 署名单位: University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9810
• DOI: 10.1126/science.adj5996
• 发表日期: 2024-03-15
• 页码: 1252-1259
• 关键词: dorsal raphe nucleus; antidepressant drugs; conditioned fear; startle; neurogenesis; inhibition; fluoxetine; veterans; BEHAVIOR; ANXIETY

摘要

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 gamma-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.