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Nat Commun ; 15(1): 5522, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951506

RESUMO

Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity (ELA). A population of neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed to be key in processing threat of different intensities to mediate active fear expression. Here, we use in vivo fiber photometry to show that ELA results in sex-specific changes in the activity of CeAL CRF+ neurons, yielding divergent mechanisms underlying the augmented startle in ELA mice, a translationally relevant behavior indicative of heightened threat reactivity and hypervigilance. Further, chemogenic inhibition of CeAL CRF+ neurons selectively diminishes startle and produces a long-lasting suppression of threat reactivity. These findings identify a mechanism for sex-differences in susceptibility for anxiety following ELA and have broad implications for understanding the neural circuitry that encodes and gates the behavioral expression of fear.


Assuntos
Ansiedade , Núcleo Central da Amígdala , Hormônio Liberador da Corticotropina , Medo , Neurônios , Reflexo de Sobressalto , Animais , Hormônio Liberador da Corticotropina/metabolismo , Medo/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Camundongos , Feminino , Masculino , Ansiedade/fisiopatologia , Núcleo Central da Amígdala/metabolismo , Reflexo de Sobressalto/fisiologia , Camundongos Endogâmicos C57BL , Comportamento Animal/fisiologia , Estresse Psicológico
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