Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening.

Marcus DJ, Bedse G, Gaulden AD, Ryan JD, Kondev V, Winters ND, Rosas-Vidal LE, Altemus M, Mackie K, Lee FS, Delpire E, Patel S
Neuron. 2020 105 (6): 1062-1076.e6

PMID: 31948734 · DOI:10.1016/j.neuron.2019.12.024

Functional coupling between the amygdala and the dorsomedial prefrontal cortex (dmPFC) has been implicated in the generation of negative affective states; however, the mechanisms by which stress increases amygdala-dmPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here, we show that the mouse basolateral amygdala (BLA)-prelimbic prefrontal cortex (plPFC) circuit is engaged by stress and activation of this pathway in anxiogenic. Furthermore, we demonstrate that acute stress exposure leads to a lasting increase in synaptic strength within a reciprocal BLA-plPFC-BLA subcircuit. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-plPFC synapses and the functional collapse of multimodal 2-AG signaling as a molecular mechanism leading to persistent circuit-specific synaptic strengthening and anxiety-like behaviors after stress exposure. These data suggest that circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and plPFC and the translation of environmental stress to affective pathology.

Copyright © 2019 Elsevier Inc. All rights reserved.

MeSH Terms (14)

Animals Anxiety Arachidonic Acids Basolateral Nuclear Complex Endocannabinoids Glutamic Acid Glycerides Male Mice Neural Pathways Prefrontal Cortex Restraint, Physical Stress, Psychological Synaptic Transmission

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