4.4 Article

αCaMKII in the lateral amygdala mediates PTSD-Like behaviors and NMDAR-Dependent LTD

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NEUROBIOLOGY OF STRESS
卷 15, 期 -, 页码 -

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.ynstr.2021.100359

关键词

Posttraumatic stress disorder (PTSD); alpha CaMKII; Cued fear conditioning; LTD; Anxiety; Amygdala

资金

  1. National Natural Science Foundation of China [31771177, 31471077, 31970944]
  2. 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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