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 (αCaMKII) in the lateral amygdala (LA). Consistently, increasing αCaMKII 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 αCaMKII 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 αCaMKII 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.

创伤后应激障碍（PTSD）是一种精神疾病，它折磨着许多人。然而，其分子和细胞机制在很大程度上仍未得到探索。在这里，我们发现 PTSD 易感小鼠表现出显着的 α-Ca ²⁺上调外侧杏仁核 (LA) 中的 /钙调蛋白依赖性激酶 II (αCaMKII)。一致地，增加 LA 中的 αCaMKII 不仅会导致 PTSD 样行为，例如恐惧消退受损和焦虑样行为，而且还会减弱 N-甲基-D-天冬氨酸受体（NMDAR）依赖的丘脑长期抑郁（LTD） -外侧杏仁核 (T-LA) 突触，并减少 GluA1-Ser845/Ser831 去磷酸化和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体 (AMPAR) 内化。将升高的 αCaMKII 抑制到正常水平可以完全挽救 PTSD 样行为和 LTD、GluA1-Ser845/Ser831 去磷酸化和 AMPAR 内化的损伤。有趣的是，GluA1-Ser845/Ser831 去磷酸化和 AMPAR 内化的缺陷不仅在恐惧消退受损后，而且在 LTD 减弱后也被检测到。我们的结果表明 LA 中的 αCaMKII 可能是 PTSD 的潜在分子决定因素。我们首次进一步证明 GluA1-Ser845/Ser831 去磷酸化和 AMPAR 内化是恐惧消退和 LTD 之间的分子联系。