2. Academic Validation
  3. A brainstem-central amygdala circuit underlies defensive responses to learned threats

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.
Yiran Gu 1 2 3,  Walter T Piper 2,  Lauren A Branigan 2,  Elena M Vazey 4,  Gary Aston-Jones 5,  Longnian Lin 1,  Joseph E LeDoux 6 7 8,  Robert M Sears 9 10 11
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), Institute of Brain Functional Genomics, School of Life Science, NYU-ECNU Institute of Brain and Cognitive Science, East China Normal University, Shanghai, China.
  • 2 Center for Neural Science, New York University, New York, NY, USA.
  • 3 Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
  • 4 Department of Biology, University of Massachusetts, Amherst, MA, USA.
  • 5 Brain Health Institute, Rutgers University/Rutgers Biomedical and Health Sciences, Piscataway, NJ, USA.
  • 6 Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), Institute of Brain Functional Genomics, School of Life Science, NYU-ECNU Institute of Brain and Cognitive Science, East China Normal University, Shanghai, China. ledoux@cns.nyu.edu.
  • 7 Center for Neural Science, New York University, New York, NY, USA. ledoux@cns.nyu.edu.
  • 8 Emotional Brain Institute, The Nathan Kline Institute, Orangeburg, NY, USA. ledoux@cns.nyu.edu.
  • 9 Center for Neural Science, New York University, New York, NY, USA. robert.sears@nki.rfmh.org.
  • 10 Emotional Brain Institute, The Nathan Kline Institute, Orangeburg, NY, USA. robert.sears@nki.rfmh.org.
  • 11 Department of Child and Adolescent Psychiatry, New York University Langone School of Medicine, New York, NY, USA. robert.sears@nki.rfmh.org.
PMID: 31758092 DOI: 10.1038/s41380-019-0599-6
Abstract

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.

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