Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress
Summary: 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....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724003280 |
| _version_ | 1797246812698968064 |
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| author | Minseok Jeong Jin-Hyeok Jang Seo-Jin Oh Jeongrak Park Junseop Lee Sehyeon Hwang Yong-Seok Oh |
| author_facet | Minseok Jeong Jin-Hyeok Jang Seo-Jin Oh Jeongrak Park Junseop Lee Sehyeon Hwang Yong-Seok Oh |
| author_sort | Minseok Jeong |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-24T19:48:45Z |
| format | Article |
| id | doaj.art-b1262412e73b45e4a0e1096863c5d0c1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T19:48:45Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b1262412e73b45e4a0e1096863c5d0c12024-03-25T04:17:29ZengElsevierCell Reports2211-12472024-04-01434114000Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stressMinseok Jeong0Jin-Hyeok Jang1Seo-Jin Oh2Jeongrak Park3Junseop Lee4Sehyeon Hwang5Yong-Seok Oh6Department of Brain Sciences, Daegu-Gyeongbuk Institute of Science and Technology, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu-Gyeongbuk Institute of Science and Technology, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu-Gyeongbuk Institute of Science and Technology, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu-Gyeongbuk Institute of Science and Technology, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu-Gyeongbuk Institute of Science and Technology, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu-Gyeongbuk Institute of Science and Technology, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu-Gyeongbuk Institute of Science and Technology, Hyeonpung-eup, Dalseong-gun, Daegu 42988, Republic of Korea; Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute, 61 Cheomdan-ro, Daegu 41062, Republic of Korea; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724003280CP: Neuroscience |
| spellingShingle | Minseok Jeong Jin-Hyeok Jang Seo-Jin Oh Jeongrak Park Junseop Lee Sehyeon Hwang Yong-Seok Oh Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress Cell Reports CP: Neuroscience |
| title | Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress |
| title_full | Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress |
| title_fullStr | Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress |
| title_full_unstemmed | Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress |
| title_short | Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress |
| title_sort | maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724003280 |
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