The neural mechanism of the different sub-regions of hippocampus involved in post-traumatic stress disorder

Abstract

post-traumatic stress disorder (PTSD), under water trauma (UWT) model rats, long-term depression, alpha calcium/calmodulin-dependent protein kinase II (αCaMKII) Post-traumatic stress disorder (PTSD) patients have severe fear extinction disorder, but the underlying molecular and neurobiological mechanisms are still unknown. The hippocampus has sub-regional specific functions, however, their involvement in PTSD is unclear. In this study, we used under water trauma (UWT) model rats which exhibit multiple core PTSD symptoms, including anxiety, depression, and impaired fear extinction. In the dorsal or ventral hippocampus, we found that long-term depression at Schaffer collateral and medial perforant pathway were impaired in UWT model rats. Moreover, although the expression levels of ionotropic glutamate receptors including NR2A, NR2B, GluA1, and GluA2 were normal, the activity of alpha calcium/calmodulin-dependent protein kinase II (αCaMKII) significantly increased in both the dorsal and ventral hippocampus of UWT model rats. These findings reveal similar abnormalities in synaptic plasticity and αCaMKII activity in different hippocampal sub-regions of UWT rats. Our results shed light on the regionspecific role of the hippocampus in PTSD and provide a theoretical basis for the development of specific treatments for PTSD.

Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders

“…Cajal first noticed the difference in HPC across the dorsoventral axis and divided the HPC into the dorsal hippocampus (dHPC) and vHPC in 1901. The HPC is regionally specific in function, with different regions playing different roles in cognition and emotion (Zuo et al, 2022 ). There is substantial evidence that the dHPC is involved in spatial memory, while the vHPC is strongly associated with stress and emotion (Fanselow and Dong, 2010 ).…”

“…Compared to wild-type rats, LTD of the Schaffer collaterals branch pathway and the HPC perforant pathway were significantly reduced in the vHPC and dHPC of UWT rats. Therefore, impaired LTD of the HPC pathway may be necessary for impaired fear extinction (Zuo et al, 2022 ).…”

“…The model mimics people's fear when their safety is threatened and is closer to the pathogenesis of psychiatric disorders such as phobias. Recently, Richter-Levin has developed an underwater trauma (UWT) model that is more consistent with the symptoms of trauma and stress disorders and has been used to study the neural mechanisms of different subregions and circuits of the HPC during fear extinction (Richter-Levin, 1998 ; Zuo et al, 2022 ).…”