Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening
| Autor: | Ken Mackie, Nathan D. Winters, James D. Ryan, Eric Delpire, Sachin Patel, Megan Altemus, David J. Marcus, Gaurav Bedse, Andrew D. Gaulden, Luis Eduardo Rosas-Vidal, Francis S. Lee, Veronika Kondev |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Restraint Physical 0301 basic medicine 2-Arachidonoylglycerol Glutamic Acid Prefrontal Cortex Arachidonic Acids Optogenetics Anxiety Synaptic Transmission Amygdala Article Glycerides Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neural Pathways medicine Animals Prefrontal cortex Basolateral Nuclear Complex General Neuroscience Glutamate receptor Endocannabinoid system 030104 developmental biology medicine.anatomical_structure chemistry Anxiogenic Accidental Falls Neuroscience Stress Psychological 030217 neurology & neurosurgery Basolateral amygdala Endocannabinoids Signal Transduction |
| Zdroj: | Neuron |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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