Neuronal activity patterns associated with a traumatic experience in PTSD-vulnerable and -resilient mice

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Posttraumatic stress disorder (PTSD) is a clinical condition that can develop when an individual is exposed to a traumatic event, leading to significant social, occupational and interpersonal impairment. Although many individuals experience at least one traumatic event in their lifetime, only a subset of around 10 to 20% of these develop PTSD. This suggests the existence of inter-individual differences in vulnerability to developing psychopathology after trauma exposure. Discovering the exact neurobiological nature of these differences may be key to understanding the factors that constitute PTSD resilience, ultimately enabling the development of new treatment options. In this study we use an established mouse model for PTSD induction that employs a battery of behavioral tests to differentiate between subgroups of mice that show varying degrees of PTSD symptomatology after trauma exposure. Since re-experiencing of traumatic memories forms a core feature of PTSD, it is interesting to study the neuronal activity patterns that are induced by a specific traumatic experience and that are likely to be involved in the formation of a trauma memory trace. By coupling a fluorescent molecular label to the promoter of the immediate-early gene Arc, neurons that are active in these mice during trauma exposure can be labeled. In our study, we try to investigate 1) if neuronal activation patterns during trauma exposure differ between the PTSD-like and resilient mice, 2) if the neurons that are activated during trauma exposure are re-activated during subsequent re-exposure to the trauma environment and 3) whether both subgroups of mice differed from each other in neuronal type and distribution in the hippocampus. Neuronal activation during trauma exposure did not differ between PTSD-like and resilient mice, but during re-exposure to the trauma environment PTSD-like mice showed significantly less neuronal activation in both the dorsal and ventral hippocampus. A small percentage of neurons that were activated during trauma exposure were re-activated during re-exposure to the trauma environment, although this only significantly differed between both subgroups of mice in the ventral inferior dentate gyrus. This suggests that PTSD-like and resilient mice did not differ in fear memory encoding, but did so in memory recall. To investigate whether PTSD-like and resilient mice differed from each other in the type of interneurons that were present, brain slices of these mice were stained for the GABAergic cell markers parvalbumin and somatostatin. PTSD-like mice showed significantly more parvalbumin positive cells in the ventral CA1, while the number of somatostatin positive cells in the dorsal dentate gyrus and dorsal CA1 was significantly reduced when compared to resilient mice, suggesting an altered inhibitory network between these subgroups of mice.
Faculteit der Sociale Wetenschappen