Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress.
Cell Rep
; 43(4): 114000, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38527063
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transtornos de Estresse Pós-Traumáticos
/
Giro Denteado
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article