Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 6, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2019409118
Keywords
depression; AMPAR; chronic stress; pBLA-vCA1; CBD
Categories
Funding
- National Key R&D Program of China [2017YFE0103400]
- National Natural Science Foundation of China [31771125, 31790911, 81521063]
- China Postdoctoral Science Foundation [2020M670059]
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Chronic unpredictable mild stress can induce depressive-like traits in mice, and activation of the posterior basal lateral amygdala to ventral CA1 innervation can reverse some neural changes and alleviate depressive behaviors.
Chronic stress is one of the most critical factors in the onset of depressive disorders; hence, environmental factors such as psychosocial stress are commonly used to induce depressive-like traits in animal models of depression. Ventral CA1 (vCA1) in hippocampus and basal lateral amygdala (BLA) are critical sites during chronic stress-induced alterations in depressive subjects; however, the underlying neural mechanisms remain unclear. Here we employed chronic unpredictable mild stress (CUMS) to model depression in mice and found that the activity of the posterior BLA to vCA1 (pBLA-vCA1) innervation was markedly reduced. Mice subjected to CUMS showed reduction in dendritic complexity, spine density, and synaptosomal AMPA receptors (AMPARs). Stimulation of pBLA-vCA1 innervation via chemogenetics or administration of cannabidiol (CBD) could reverse CUMS-induced synaptosomal AMPAR decrease and efficiently alleviate depressive-like behaviors in mice. These findings demonstrate a critical role for AMPARs and CBD modulation of pBLA-vCA1 innervation in CUMS-induced depressive-like behaviors.
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