On April 4, 2025, Professor Chen Zhong and Researcher Wang Yi’s team from Zhejiang Chinese Medical University (ZCMU) published research in the well-known journal Science Advances titled “Cholinergic signaling to CA1 astrocytes controls fear extinction”. The research reveals the role and mechanism of hippocampal CA1 astrocytes mediated by basal fore-brain cholinergic signaling in the manipulation of fear extinction. It may provide a promising target for the treatment of Post-Traumatic Stress Disorder (PTSD) and fear- and anxiety-related disorders.

Fear extinction refers to a biological process in which learned fear memory diminishes through repeated exposure to previous fear contexts or cues (in the absence of an aversive stimulus). Its deficits can lead to various psychiatric disorders, such as PTSD and anxiety disorder. Therefore, it underscores the urgent need to explore the critical mechanism and contributors of fear extinction in-depth, paving the way for new therapeutic strategies targeting diseases related to fear memory.

This research sheds new light on the novel mechanism by which “cholinergic neuron-astrocytes” interaction diminishes the fear memory. The findings may not only identify promising targets for fear- and anxiety-related psychiatric disorders but also provide a new approach to repurposing donepezil for fear and anxiety disorders.

The first author of the research is Li Yulan, an Associate Researcher from the School of Basic Medical Sciences, ZCMU. Dr. Li Lixuan from the Department of Neurology, the Second Affiliated Hospital Zhejiang University School of Medicine (SAHZU), and postgraduate Wang Yibei from the School of Pharmaceutical Sciences at ZCMU, are the co-first authors. Professor Chen Zhong and Researcher Wang Yi are the corresponding authors. In addition to the support and guidance from Academicians Duan Shumin and Vladimir Parpura, the research is also supported by the National Key Research and Development Plan, the National Natural Science Foundation of China, and the Zhejiang Provincial Natural Science Foundation.