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Cell Reports
년도 2024
학술지명 Cell Reports
논문명 Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress
저자명 Minseok Jeong, Jin-Hyeok Jang, Seo-Jin Oh, Jeongrak Park, Junseop Lee, Sehyeon Hwang, Yong-Seok Oh
Link 관련링크 759회 연결

Fear overgeneralization is a maladaptive response to traumatic stress that is associated with the inability to discriminate between threat and safety contexts, a hallmark feature of post-traumatic stress disorder (PTSD). However, the neural mechanisms underlying this deficit remain unclear. Here, we show that traumatic stress exposure impairs contextual discrimination between threat and safety contexts in the learned helplessness (LH) model. Mossy cells (MCs) in the dorsal hippocampus are suppressed in response to traumatic stress. Bidirectional manipulation of MC activity in the LH model reveals that MC inhibition is causally linked to impaired contextual discrimination. Mechanistically, MC inhibition increases the number of active granule cells in a given context, significantly overlapping context-specific ensembles. Our study demonstrates that maladaptive inhibition of MCs after traumatic stress is a substantial mechanism underlying fear overgeneralization with contextual discrimination deficit, suggesting a potential therapeutic target for cognitive symptoms of PTSD.