How The EndoCannabinoid System Controls Stress And Anxiety | Cannabinoid Tone In The Brain | FPS #6

Endocannabinoids - cannabinoids made in the body, by the body - are a Hot Topic in Neuroscience & Beyond - with Western & integrative medicine coming to embrace the role of these important compounds, the EndoCannabinoid system is emerging as a therapeutic target for treatment of several psychiatric disorders. However, endocannabinoid system research is limited by scientists' ability to translate these groundbreaking research discoveries into clinical treatments, mostly due to a lack of understanding of how this system is involved with basic physiological processes, including stress & anxiety.

In this episode, Dr. David Marcus - A recent graduate of the Neuroscience PhD Program at Vanderbilt University & 1st author of this episode's manuscript - joins us to speak about the recently published manuscript, "Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening", published in the journal Neuron.
https://www-sciencedirect-com.proxy1.lib.uwo.ca/science/article/pii/S0896627319310906

Highlights
• The BLA-plPFC circuit is engaged by stress exposure and its activation is anxiogenic
•Stress enhances glutamate release in a reciprocal BLA-plPFC-BLA subcircuit
•BLA-plPFC glutamatergic drive is constrained by multimodal 2-AG signaling
•2-AG signaling collapse mediates stress-induced circuit strengthening and anxiety

Abstract
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.

Keywords
2-arachidonoylglycerol, glutamate, prefrontal cortex, anxiety, cannabinoid, amygdala, stress, optogenetics, cannabis, post traumatic stress disorder.

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