The role of hippocampal CaMKII in resilience to trauma-related psychopathology

Somoday Hazra, Joyeeta Dutta Hazra, Rani Amit Bar-On, Yanhong Duan, Shahaf Edut, Xiaohua Cao, Gal Richter-Levin

Research output: Contribution to journalArticlepeer-review

Abstract

Traumatic stress exposure can form persistent trauma-related memories. However, only a minority of individuals develop post-traumatic stress disorder (PTSD) symptoms upon exposure. We employed a rat model of PTSD, which enables differentiating between exposed-affected and exposed-unaffected individuals. Two weeks after the end of exposure, male rats were tested behaviorally, following an exposure to a trauma reminder, identifying them as trauma 'affected' or 'unaffected.' In light of the established role of hippocampal synaptic plasticity in stress and the essential role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in hippocampal based synaptic plasticity, we pharmacologically inhibited CaMKII or knocked-down (kd) αCaMKII (in two separate experiments) in the dorsal dentate gyrus of the hippocampus (dDG) following exposure to the same trauma paradigm. Both manipulations brought down the prevalence of 'affected' individuals in the trauma-exposed population. A day after the last behavioral test, long-term potentiation (LTP) was examined in the dDG as a measure of synaptic plasticity. Trauma exposure reduced the ability to induce LTP, whereas, contrary to expectation, αCaMKII-kd reversed this effect. Further examination revealed that reducing αCaMKII expression enables the formation of αCaMKII-independent LTP, which may enable increased resilience in the face of a traumatic experience. The current findings further emphasize the pivotal role dDG has in stress resilience.

Original languageEnglish
Article number100506
JournalNeurobiology of Stress
Volume21
DOIs
StatePublished - Nov 2022

Bibliographical note

Funding Information:
This research was supported by MOST China-Israel cooperation (No: 2016YFE0130500 ) grant 3-13563 to GR-L & XH, by research grant from the State of Israel Ministry of Science, Technology, & Space to GR-L, by research grant 3-14356 from the State of Israel Ministry of Science, Technology, & Space to GR-L.

Publisher Copyright:
© 2022 The Authors

Keywords

  • CaMKII
  • Dentate gyrus
  • Long-term potentiation
  • PTSD
  • Stress resilience

ASJC Scopus subject areas

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

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