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

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) alpha CaMKII (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, alpha CaMKII-kd reversed this effect. Further examination revealed that reducing alpha CaMKII expression enables the formation of alpha CaMKII-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.

Automated summary

Traumatic stress exposure can lead to persistent trauma-related memories. In this study, a rat model of PTSD was used to differentiate between individuals affected and unaffected by trauma. Inhibiting CaMKII or reducing alpha CaMKII expression in the hippocampus resulted in a decrease in the number of affected individuals. Additionally, reducing alpha CaMKII expression facilitated the formation of alpha CaMKII-independent LTP, potentially enhancing resilience in the face of trauma.