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

Nat Commun. 2020 Jan 22;11(1):422. doi: 10.1038/s41467-020-14393-y.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Central Amygdaloid Nucleus / cytology
  • Central Amygdaloid Nucleus / metabolism*
  • Conditioning, Psychological
  • Corticotropin-Releasing Hormone / metabolism*
  • Extinction, Psychological*
  • Fear*
  • Female
  • Male
  • Memory
  • Neurons / metabolism*


  • Corticotropin-Releasing Hormone