Up-Regulation of αCaMKII Impairs Cued Fear Extinction and NMDAR-Dependent LTD in the Lateral Amygdala

Abstract

Impaired fear extinction is one of the hallmark symptoms of post-traumatic stress disorder (PTSD). The roles of αCaMKII have been not extensively studied in fear extinction and LTD. Here, we found PTSD susceptible mice exhibited significant up-regulation of αCaMKII in the lateral amygdala (LA). Consistently, increasing αCaMKII in LA profoundly not only caused PTSD-like symptoms such as impaired fear extinction and anxiety-like behaviors, but also attenuated NMDAR-dependent LTD at thalamo-LA synapses, reduced GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization. Suppressing the elevated αCaMKII to normal level could completely reverse both PTSD-like symptoms and the impairments in LTD, GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization. Intriguingly, deficits in AMPAR internalization and GluA1-Ser845/Ser831 dephosphorylation were detected not only after impaired fear extinction, but also after attenuated LTD Our results demonstrate for the first time GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization are molecular links between LTD and fear extinction, and suggest αCaMKII may be a potential molecular determinant of PTSD.