Dominant activities of fear engram cells in the dorsal dentate gyrus underlie fear generalization in mice

• DOI: 10.1371/journal.pbio.3002679
• Publication Date: 2024-07-12T17:38:17Z
• Authors: Kun Cui; Xuetao Qi; Zilong Liu; Weiqi Sun; Peijie Jiao; Chang Liu; Jifu Tong; Xiaoyan Sun; Haojie Sun; Su Fu; Jiaxin Wang; Yawen Zheng; Tianyu Liu; Shuang Cui; Fengyu Liu; Jian Mao; Jie Zheng; You Wan; Ming Yi
• Keywords: Engram

Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play crucial role in accurate memory retrieval. However, the coordination mechanism neuronal subpopulations within dDG network during generalization not well understood. Here, with Tet-off system combined immunostaining two-photon calcium imaging, we report labeled conditioned context constitutes significantly higher proportion neurons activated similar where mice show generalized fear. activation these encoding both sufficient necessary for inducing context. Activities mossy ventral (vMCs) are suppressed showing context, activating vMCs-dDG pathway suppresses but Finally, modifying engrams “safety” signals effectively rescues generalization. These findings reveal competitive advantage underlies generalization, which can be rescued by engrams, provide novel insights into as basis