Abstract
Only a minority of individuals experiencing trauma subsequently develop post-traumatic stress disorder (PTSD). However, whether differences in vulnerability to PTSD result from a predisposition or trauma exposure remains unclear. A major challenge in differentiating these possibilities is that clinical studies focus on individuals already exposed to trauma without pre-trauma conditions. Here, using the predator scent model of PTSD in rats and a longitudinal design, we measure pre-trauma brain-wide neural circuit functional connectivity, behavioral and corticosterone responses to trauma exposure, and post-trauma anxiety. Freezing during predator scent exposure correlates with functional connectivity in a set of neural circuits, indicating pre-existing circuit function can predispose animals to differential fearful responses to threats. Counterintuitively, rats with lower freezing show more avoidance of the predator scent, a prolonged corticosterone response, and higher anxiety long after exposure. This study provides a framework of pre-existing circuit function that determines threat responses, which might directly relate to PTSD-like behaviors.
Highlights
A minority of individuals experiencing trauma subsequently develop post-traumatic stress disorder (PTSD)
We find that individual differences in behavior and neural circuit function prior to trauma exposure predict animals’ susceptibility to developing PTSD-like behaviors
We found that animals displayed large differences in freezing behavior during fox-urine exposure
Summary
A minority of individuals experiencing trauma subsequently develop post-traumatic stress disorder (PTSD). It has been suggested that vulnerability to PTSD may result from individual differences in early life events, pre-existing conditions, or responses to trauma exposure[1,2,3]. Some studies suggest that PTSD-related decreases in hippocampal volume might be a consequence of traumatic events and PTSD development, whereas other studies showed that PTSD patients’ twins who did not have a trauma experience had smaller hippocampal volumes, suggesting that reduced hippocampal volume may predispose individuals to developing PTSD4– 7 These conflicting results are reported in studies of cortisol levels and brain activity in relation to PTSD8–10, which together contribute to our elusive understanding of individual vulnerability to PTSD. Among many stress paradigms that have been used to produce rat models of PTSD, predator scent exposure in an inescapable environment is a commonly used psychological stressor[12] This method mimics a life-threatening situation that is ecologically relevant and physically innocuous, preventing confounding effects of inflammation or pain due to injury. Whether behavioral responses to predator scent is a useful indicator of subsequent development of PTSD is unknown
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