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Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening

63 Pages Posted: 30 May 2019 Sneak Peek Status: Review Complete

See all articles by David J. Marcus

David J. Marcus

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

Gaurav Bedse

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

Andrew Gaulden

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

James D. Ryan

Cornell University, Weill Cornell Medical College, Department of Psychiatry

Jacqueline Clauss

Harvard University - Massachusetts General Hospital

Eric Delpire

Vanderbilt University

Francis S. Lee

Cornell University, Weill Cornell Medical College, Department of Psychiatry

Jennifer Blackford

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

Sachin Patel

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

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Abstract

Functional coupling between the basolateral amygdala (BLA) and areas of the dorsal prefrontal cortex (dPFC) have been implicated in the generation of negative affective states under stressful conditions; however, the synaptic and molecular mechanisms by which stress increases BLA-dPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here we show that BLA-dPFC functional connectivity is enhanced under conditions of potential threat and correlates with trait anxiety in humans and that acute stress exposure increases anxiety-like behavior and synaptic strength within a reciprocal BLA-dPFC-BLA subcircuit in mice. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-dPFC synapses and the 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 circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and dPFC and the translation of environmental stress to affective pathology.

Keywords: 2-Arachidonoylglycerol, glutamate, prefrontal cortex, anxiety, cannabinoid, amygdala

Suggested Citation

Marcus, David J. and Bedse, Gaurav and Gaulden, Andrew and Ryan, James D. and Clauss, Jacqueline and Delpire, Eric and Lee, Francis S. and Blackford, Jennifer and Patel, Sachin, Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening (May 30, 2019). NEURON-D-19-00796. Available at SSRN: https://ssrn.com/abstract=3396180 or http://dx.doi.org/10.2139/ssrn.3396180
This is a paper under consideration at Cell Press and has not been peer-reviewed.

David J. Marcus

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

United States

Gaurav Bedse

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

United States

Andrew Gaulden

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

United States

James D. Ryan

Cornell University, Weill Cornell Medical College, Department of Psychiatry

1300 York Avenue
New York, NY
United States

Jacqueline Clauss

Harvard University - Massachusetts General Hospital

55 Fruit Street Boston
Boston, MA 02114
United States

Eric Delpire

Vanderbilt University

2301 Vanderbilt Place
Nashville, TN 37240
United States

Francis S. Lee

Cornell University, Weill Cornell Medical College, Department of Psychiatry ( email )

1300 York Avenue
New York, NY
United States

Jennifer Blackford

Vanderbilt University - Department of Psychiatry and Behavioral Sciences

United States

Sachin Patel (Contact Author)

Vanderbilt University - Department of Psychiatry and Behavioral Sciences ( email )

United States

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