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Endocannabinoid Release at Ventral Hippocampal-Amygdala Synapses Regulates Stress-Induced Behavioral Adaptation

46 Pages Posted: 31 Jan 2023 Publication Status: Published

See all articles by Veronika Kondev

Veronika Kondev

Vanderbilt University - Vanderbilt Brain Institute

Mustafa Najeed

Vanderbilt University - Vanderbilt Brain Institute

Farhana Yasmin

Northwestern University - Northwestern Center for Psychiatric Neuroscience

Amanda Morgan

Northwestern University - Northwestern Center for Psychiatric Neuroscience

Niharika Loomba

Vanderbilt University - Vanderbilt Brain Institute

Keenan Johnson

Northwestern University - Northwestern Center for Psychiatric Neuroscience

Danielle Adank

Vanderbilt University - Vanderbilt Brain Institute

Ao Dong

Peking University - State Key Laboratory of Membrane Biology

Eric Delpire

Vanderbilt University - Department of Anesthesiology

Yulong Li

Peking University - State Key Laboratory of Membrane Biology

Danny G. Winder

Vanderbilt University - Department of Molecular Physiology and Biophysics; Vanderbilt University - Department of Pharmacology

Brad Grueter

Vanderbilt University - Department of Anesthesiology; Vanderbilt University - Department of Pharmacology

Sachin Patel

Northwestern University - Northwestern Center for Psychiatric Neuroscience; Northwestern University - Department of Psychiatry and Behavioral Sciences

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Abstract

The endocannabinoid (eCB) system is a key modulator of glutamate release within limbic neurocircuitry and is heavily implicated in the modulation of stress responsivity and adaptation. The ventral hippocampus (vHPC)–basolateral amygdala (BLA) circuit has been previously implicated in the expression of negative affective states following stress exposure and is modulated by retrograde eCB signaling. However, the mechanism governing eCB release, and whether eCB signaling within vHPC-BLA circuits is causally related to stress-induced affective pathology, are not known. Here we utilized in vivo optogenetic- and biosensor-based approaches to reveal the temporal dynamics of BLA neuron activity-dependent and stress-induced eCB release at vHPC-BLA synapses. Furthermore, we demonstrate that genetic deletion of cannabinoid type-1 receptors selectively at vHPC-BLA synapses decreases active coping responses to acute stressors and exacerbates subsequent anxiety- and depressive-like phenotypes. These data reveal novel insight into in vivo determinants of eCB release at limbic synapses and suggest eCB signaling within the vHPC-BLA circuit serves to counteract adverse behavioral consequences of stress exposure.

Note:
Funding Information: These studies were supported by NIH grants MH107435 (S.P.) and MH119817 (S.P.).

Declaration of Interests: SP is a scientific consultant for Psy Therapeutics, Janssen Pharmaceuticals, and Jazz Pharmaceuticals unrelated to the present work. All other authors declare no conflicts of interest.

Ethics Approval Statement: All experiments were approved by the Vanderbilt University Institutional Animal Care and Use Committees and were conducted in accordance with the National Institute of Health guidelines for the Care and Use of Laboratory Animals.

Keywords: CB1 receptor, 2-arachidonoylglycerol, posttraumatic stress disorder, anxiety, depression, Cannabis

Suggested Citation

Kondev, Veronika and Najeed, Mustafa and Yasmin, Farhana and Morgan, Amanda and Loomba, Niharika and Johnson, Keenan and Adank, Danielle and Dong, Ao and Delpire, Eric and Li, Yulong and Winder, Danny G. and Grueter, Brad and Patel, Sachin, Endocannabinoid Release at Ventral Hippocampal-Amygdala Synapses Regulates Stress-Induced Behavioral Adaptation. Available at SSRN: https://ssrn.com/abstract=4339779 or http://dx.doi.org/10.2139/ssrn.4339779
This version of the paper has not been formally peer reviewed.

Veronika Kondev

Vanderbilt University - Vanderbilt Brain Institute ( email )

Mustafa Najeed

Vanderbilt University - Vanderbilt Brain Institute ( email )

Farhana Yasmin

Northwestern University - Northwestern Center for Psychiatric Neuroscience ( email )

Amanda Morgan

Northwestern University - Northwestern Center for Psychiatric Neuroscience ( email )

Niharika Loomba

Vanderbilt University - Vanderbilt Brain Institute ( email )

Keenan Johnson

Northwestern University - Northwestern Center for Psychiatric Neuroscience ( email )

Danielle Adank

Vanderbilt University - Vanderbilt Brain Institute ( email )

Ao Dong

Peking University - State Key Laboratory of Membrane Biology ( email )

Eric Delpire

Vanderbilt University - Department of Anesthesiology ( email )

Yulong Li

Peking University - State Key Laboratory of Membrane Biology ( email )

Beijing, 100871
China

Danny G. Winder

Vanderbilt University - Department of Molecular Physiology and Biophysics ( email )

Vanderbilt University - Department of Pharmacology ( email )

United States

Brad Grueter

Vanderbilt University - Department of Anesthesiology ( email )

Vanderbilt University - Department of Pharmacology ( email )

Sachin Patel (Contact Author)

Northwestern University - Northwestern Center for Psychiatric Neuroscience ( email )

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

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