Journal
NEUROBIOLOGY OF STRESS
Volume 15, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ynstr.2021.100359
Keywords
Posttraumatic stress disorder (PTSD); alpha CaMKII; Cued fear conditioning; LTD; Anxiety; Amygdala
Categories
Funding
- National Natural Science Foundation of China [31771177, 31471077, 31970944]
- MOST China-Israel cooperation [2016YFE0130500]
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The research discovered that PTSD susceptible mice exhibited significant up-regulation of alpha CaMKII in the lateral amygdala, leading to PTSD-like behaviors. Inhibiting alpha CaMKII levels completely rescued these behaviors and related impairments, suggesting that alpha CaMKII may be a potential molecular determinant of PTSD.
Post-traumatic stress disorder (PTSD) is a psychiatric disorder that afflicts many individuals. However, its molecular and cellular mechanisms remain largely unexplored. Here, we found PTSD susceptible mice exhibited significant up-regulation of alpha-Ca2+/calmodulin-dependent kinase II (alpha CaMKII) in the lateral amygdala (LA). Consistently, increasing alpha CaMKII in the LA not only caused PTSD-like behaviors such as impaired fear extinction and anxiety-like behaviors, but also attenuated N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) at thalamo-lateral amygdala (T-LA) synapses, and reduced GluA1-Ser845/Ser831 dephosphorylation and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization. Suppressing the elevated alpha CaMKII to normal levels completely rescued both PTSD-like behaviors and the impairments in LTD, GluA1-Ser845/Ser831 dephosphorylation, and AMPAR internalization. Intriguingly, deficits in GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization were detected not only after impaired fear extinction, but also after attenuated LTD. Our results suggest that alpha CaMKII in the LA may be a potential molecular determinant of PTSD. We further demonstrate for the first time that GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization are molecular links between fear extinction and LTD.
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