A brainstem-central amygdala circuit underlies defensive responses to learned threats

Mol Psychiatry. 2020 Mar;25(3):640-654. doi: 10.1038/s41380-019-0599-6. Epub 2019 Nov 22.


Norepinephrine (NE) plays a central role in the acquisition of aversive learning via actions in the lateral nucleus of the amygdala (LA) [1, 2]. However, the function of NE in expression of aversively-conditioned responses has not been established. Given the role of the central nucleus of the amygdala (CeA) in the expression of such behaviors [3-5], and the presence of NE axons projections in this brain nucleus [6], we assessed the effects of NE activity in the CeA on behavioral expression using receptor-specific pharmacology and cell- and projection-specific chemogenetic manipulations. We found that inhibition and activation of locus coeruleus (LC) neurons decreases and increases freezing to aversively conditioned cues, respectively. We then show that locally inhibiting or activating LC terminals in CeA is sufficient to achieve this bidirectional modulation of defensive reactions. These findings support the hypothesis that LC projections to CeA are critical for the expression of defensive responses elicited by conditioned threats.

Publication types

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

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Basolateral Nuclear Complex / physiology
  • Brain Stem / physiology
  • Central Amygdaloid Nucleus / physiology*
  • Conditioning, Classical / physiology
  • Fear / physiology
  • Locus Coeruleus / metabolism
  • Male
  • Neurons / metabolism
  • Norepinephrine / metabolism
  • Norepinephrine / physiology*
  • Rats
  • Rats, Sprague-Dawley


  • Norepinephrine