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

Yiran Gu, Walter T. Piper, Lauren A. Branigan, Elena M. Vazey, Gary Aston-Jones, Longnian Lin, Joseph E. LeDoux, Robert M. Sears

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)640-654
Number of pages15
JournalMolecular Psychiatry
Issue number3
StatePublished - Mar 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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