Neural Mechanisms Underlying Resistance to Conditioned Defeat

Social stress is an important factor in the onset of stress-related psychopathologies such as anxiety and depression. However, individuals are not equally susceptible to the long-term negative consequences of exposure to traumatic events. In order to fully understand the development of stress-induced behavioral changes, we must understand individual variability in stress vulnerability. The ventral medial prefrontal cortex (vmPFC) controls executive functions such as working memory, decision making, inhibitory response control, and attention shifting. Previous work in several models of experience-dependent resistance to stress implicates the vmPFC as a key substrate in resiliency. Conditioned defeat is a model in male Syrian hamsters (Mesocricetus auratus) in which normal territorial aggression is replaced by increased submissive and defensive behavior following social defeat. We have previously shown that dominant males show a reduced conditioned defeat response compared to subordinates and controls. We hypothesized that defeat-induced activation of vmPFC cells that project to the basolateral amygdala (BLA) is necessary to confer resistance to conditioned defeat in dominant individuals. First, we investigated the effect of social status on defeat-induced neural activation. We found that dominants had more c-Fos immunopositive cells in the vmPFC following social defeat than did subordinates. Second, we investigated whether defeat-induced vmPFC activation was necessary for resistance to conditioned defeat in dominants. We found that pharmacological inactivation of the vmPFC during social defeat increased the conditioned defeat response in dominants compared to vehicle controls. Third, we investigated the functional connectivity of the vmPFC neurons by investigating the possibility that the vmPFC neurons activated by social defeat project directly to the BLA, a brain region known to be critical for the acquisition and expression of conditioned defeat. While the results of the third study were inconclusive, we are able to provide suggestions for future tract tracing studies. Altogether, these data suggest that neural activation in the vmPFC plays a critical role in the resistance to conditioned defeat experienced by dominant individuals.