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

Yong S. Jo, Vijay Mohan K. Namboodiri, Garret D. Stuber and Larry S. Zweifel ()
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Yong S. Jo: University of Washington
Vijay Mohan K. Namboodiri: University of Washington
Garret D. Stuber: University of Washington
Larry S. Zweifel: University of Washington

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14393-y

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