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

Shuming An, Jiayue Wang, Xuliang Zhang, Yanhong Duan, Yiqiong Xu, Junyan Lv, Dasheng Wang, Huan Zhang, Gal Richter-Levin, Oded Klavir, Buwei Yu, Xiaohua Cao

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number100359
JournalNeurobiology of Stress
Volume15
DOIs
StatePublished - Nov 2021

Bibliographical note

Publisher Copyright:
© 2021

Keywords

  • Amygdala
  • Anxiety
  • Cued fear conditioning
  • LTD
  • Posttraumatic stress disorder (PTSD)
  • αCaMKII

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Endocrinology
  • Cellular and Molecular Neuroscience
  • Molecular Biology
  • Biochemistry
  • Physiology

Fingerprint

Dive into the research topics of 'αCaMKII in the lateral amygdala mediates PTSD-Like behaviors and NMDAR-Dependent LTD'. Together they form a unique fingerprint.

Cite this