Glutamate receptor expression in the PL-BLA circuit is associated with susceptibility to showing the PTSD-like phenotype

Abstract

While many individuals experience traumatic events during their lifetimes, only some go on to develop post-traumatic stress disorder (PTSD). This susceptibility and resilience to developing PTSD can be modelled in rodents using the stress-enhanced fear learning (SEFL) procedure, in which rats are exposed to a session of massed, unpredictable footshocks and subsequently assessed on tasks of adaptive fear learning. It has previously been observed that subpopulations of rats are susceptible and resilient to showing the PTSD-like phenotype following SEFL, and that these rats show differences in glutamate receptor expression in the basolateral amygdala. However, it is currently unknown whether structural differences are observed in other brain regions implicated in stress responding and memory. Using the refined SEFL procedure, this study aimed to determine whether expression of GluN2B, GluA1 and GluA2 receptor subunits in the prelimbic and infralimbic cortices, and dorsal hippocampus could be correlated to the SEFL-phenotype or shock experience in male rats. Here we show that following SEFL, differences can be observed in receptor subunit expression in the infralimbic cortex and dorsal hippocampus as a function of shock experience, whilst differences in the prelimbic cortex are associated with susceptibility. Importantly, these structural changes can be observed in male rats that are group-housed and exposed to 13-shocks rather than 15-shocks, indicating that the refined SEFL procedure offers a robust animal analogue of the non-associative fear sensitisation that occurs in PTSD. Future studies using this procedure could pave the way to the eventual development of pharmacological treatments to alleviate or prevent stress-induced psychopathology in susceptible individuals.