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Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit.


ABSTRACT: Fear extinction is an active learning process whereby previously established conditioned responses to a conditioned stimulus are suppressed. Paradoxically, when extinction training is performed immediately following fear acquisition, the extinction memory is weakened. Here, we demonstrate that corticotrophin-releasing factor (CRF)-expressing neurons in the central amygdala (CeA) antagonize the extinction memory following immediate extinction training. CeA-CRF neurons transition from responding to the unconditioned stimulus to the conditioned stimulus during the acquisition of a fear memory that persists during immediate extinction training, but diminishes during delayed extinction training. Inhibition of CeA-CRF neurons during immediate extinction training is sufficient to promote enhanced extinction memories, and activation of these neurons following delay extinction training is sufficient to reinstate a previously extinguished fear memory. These results demonstrate CeA-CRF neurons are an important substrate for the persistence of fear and have broad implications for the neural basis of persistent negative affective behavioral states.

SUBMITTER: Jo YS 

PROVIDER: S-EPMC6976644 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit.

Jo Yong S YS   Namboodiri Vijay Mohan K VMK   Stuber Garret D GD   Zweifel Larry S LS  

Nature communications 20200122 1


Fear extinction is an active learning process whereby previously established conditioned responses to a conditioned stimulus are suppressed. Paradoxically, when extinction training is performed immediately following fear acquisition, the extinction memory is weakened. Here, we demonstrate that corticotrophin-releasing factor (CRF)-expressing neurons in the central amygdala (CeA) antagonize the extinction memory following immediate extinction training. CeA-CRF neurons transition from responding t  ...[more]

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