Diagnosis of psychiatric disorders in humans is based on comparing individuals to the normal population. However, many animal models analyze averaged group effects, thus compromising their translational power. This discrepancy is particularly relevant in posttraumatic stress disorder (PTSD), where only a minority develop the disorder following a traumatic experience. In our PTSD rat model, we utilize a novel behavioral profiling approach that allows the classification of affected and unaffected individuals in a trauma-exposed population. Rats were exposed to underwater trauma (UWT) and four weeks later their individual performances in the open field and elevated plus maze were compared to those of the control group, allowing the identification of affected and resilient UWT-exposed rats. Behavioral profiling revealed that only a subset of the UWT-exposed rats developed long-lasting behavioral symptoms. The proportion of affected rats was further enhanced by pre-exposure to juvenile stress, a well-described risk factor of PTSD. For a biochemical proof of concept we analyzed the expression levels of the GABAA receptor subunits α1 and α2 in the ventral, dorsal hippocampus and basolateral amygdala. Increased expression, mainly of α1, was observed in ventral but not dorsal hippocampus of exposed animals, which would traditionally be interpreted as being associated with the exposure-resultant psychopathology. However, behavioral profiling revealed that this increased expression was confined to exposed-unaffected individuals, suggesting a resilience-associated expression regulation. The results provide evidence for the importance of employing behavioral profiling in animal models of PTSD, in order to better understand the neural basis of stress vulnerability and resilience.

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Intrusive re-experiencing is a core symptom in post-traumatic stress disorder (PTSD), often triggered by contextual cues associated with the trauma. It is not yet clear if intrusive re-experiencing is only the result, or whether it may contribute to the establishment of PTSD following acute stress. This study aimed at examining the impact of an underwater trauma (UWT) reminder on anxiety-like behaviour and on neuronal activity and plasticity in the hippocampus and the amygdala. Sprague-Dawley rats were exposed to UWT and 24 h later were re-exposed to the context. The effects on behaviour, activation of the amygdala (BLA) and dentate gyrus (DG), and on long-term potentiation (LTP) and local circuit activity (frequency-dependent inhibition (FDI) and paired-pulse inhibition (PPI)) in the DG were assessed. The exposure to UWT by itself resulted in increased anxiety behaviour in the open field, together with increased PPI. Upon exposure to the UWT reminder, an additional increase in anxiety was also observed in the EPM and in FDI. Moreover, reminder exposure resulted in impaired DG LTP and a significant BLA extracellular-signal-regulated kinases (ERK) 2 activation. In conclusion, these observed effects of exposure to a trauma reminder, following the exposure to the initial trauma, might be associated with the progression of trauma-related pathologies and the development of related disorders.