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Persistent Activation of Central Amygdala CRF Neurons Helps Drive the Immediate Fear Extinction Deficit

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Authors: Yong S. Jo, Vijay Mohan K. Namboodiri, Garret D. Stuber, Larry S. Zweifel
Publication: Nature Communications
Date: January 22, 2020
Link to article: https://www.nature.com/articles/s41467-020-14393-y?__hssc=91116613.31.160888808…

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.

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