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

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 amy...

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Bibliographic Details
Published in:Molecular psychiatry 2020-03, Vol.25 (3), p.640-654
Main Authors: Gu, Yiran, Piper, Walter T., Branigan, Lauren A., Vazey, Elena M., Aston-Jones, Gary, Lin, Longnian, LeDoux, Joseph E., Sears, Robert M.
Format: Article
Language:English
Subjects:
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Alarm reaction
Amygdala
Animals
Anxiety
Avoidance Learning - physiology
Axons
Basolateral Nuclear Complex - physiology
Behavior
Behavioral Sciences
Biological Psychology
Brain stem
Brain Stem - physiology
Central Amygdaloid Nucleus - physiology
Child & adolescent psychiatry
Conditioning, Classical - physiology
Danger perception
Experiments
Fear - physiology
Genomics
Health aspects
Hypotheses
Limbic system
Locus coeruleus
Locus Coeruleus - metabolism
Male
Medical examination
Medicine
Medicine & Public Health
Neurons - metabolism
Neurosciences
Norepinephrine
Norepinephrine - metabolism
Norepinephrine - physiology
Pharmacotherapy
Physiological aspects
Psychiatry
Psychological aspects
Rats
Rats, Sprague-Dawley
Stainless steel
Surgery
Threats
Tonic immobility
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Summary: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.
ISSN:1359-4184
1476-5578
DOI:10.1038/s41380-019-0599-6