Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening
63 Pages Posted: 30 May 2019 Sneak Peek Status: Review CompleteMore...
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: Suggested Citation