Dysregulation of aversive signaling pathways: a novel circuit endophenotype for pain and anxiety disorders

•Midbrain and noradrenaline pathways to lateral amygdala trigger fear learning.•A parallel parabrachial-to-central amygdala circuit engages fear memory formation.•Feedback circuits engaged by learning control the strength of fear memories.•Dysregulation of aversive signaling circuits occurs in pain...

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Bibliographic Details
Published in:Current opinion in neurobiology 2018-02, Vol.48, p.37-44
Main Authors: Yeh, Li-Feng, Watanabe, Mayumi, Sulkes-Cuevas, Jessica, Johansen, Joshua P
Format: Article
Language:English
Subjects:
Animals
Anxiety Disorders - genetics
Anxiety Disorders - pathology
Anxiety Disorders - physiopathology
Avoidance Learning - physiology
Conditioning, Classical
Endophenotypes
Fear
Humans
Memory
Pain - genetics
Pain - pathology
Pain - physiopathology
Signal Transduction - physiology
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Summary:•Midbrain and noradrenaline pathways to lateral amygdala trigger fear learning.•A parallel parabrachial-to-central amygdala circuit engages fear memory formation.•Feedback circuits engaged by learning control the strength of fear memories.•Dysregulation of aversive signaling circuits occurs in pain and anxiety disorders. Aversive experiences activate dedicated neural instructive pathways which trigger memory formation and change behavior. The strength of these aversive memories and the degree to which they alter behavior is proportional to the intensity of the aversive experience. Dysregulation of aversive learning circuits can lead to psychiatric pathology. Here we review recent findings elucidating aversive instructive signaling circuits for fear conditioning. We then examine how chronic pain as well as stress and anxiety disrupt these circuits and the implications this has for understanding and treating psychiatric disease. Together this review synthesizes current work on aversive instructive signaling circuits in health and disease and suggests a novel circuit based framework for understanding pain and anxiety syndromes.
ISSN:0959-4388
1873-6882
DOI:10.1016/j.conb.2017.09.006