Abstract
The ventromedial prefrontal cortex (vmPFC) plays a critical role in stress resilience through top-down inhibition of key stress-sensitive limbic and hindbrain structures, including the dorsal raphe nucleus (DRN). In a model of experience-dependent stress resistance, socially dominant Syrian hamsters display fewer signs of anxiety following acute social defeat when compared to subordinate or control counterparts. Further, dominants activate vmPFC neurons to a greater degree during stress than do subordinates and become stress-vulnerable following pharmacological inhibition of the vmPFC. Dominants also display fewer stress-activated DRN neurons than subordinates do, suggesting that dominance experience gates activation of vmPFC neurons that inhibit the DRN during social defeat stress. To test whether social dominance alters stress-induced activity of a vmPFC-DRN pathway, we injected a retrograde tracer, cholera toxin B (CTB), into the DRN of dominant, subordinate, and control hamsters and used a dual-label immunohistochemical approach to identify vmPFC neurons co-labeled with CTB and the defeat-induced expression of an immediate early gene, cFos. Results indicate that dominant hamsters display more cFos+ and dual-labeled cells in layers V/VI of infralimbic and prelimbic subregions of the vmPFC compared to other animals. Furthermore, vmPFC-DRN activation corresponded directly with proactive behavioral strategies during defeat, which is indicative of stress resilience. Together, results suggest that recruiting the vmPFC-DRN pathway during acute stress corresponds with resistance to the effects of social defeat in dominant hamsters. Overall, these findings indicate that a monosynaptic vmPFC-DRN pathway can be engaged in an experience-dependent manner, which has implications for behavioral interventions aimed at alleviating stress-related psychopathologies.
Highlights
While exposure to traumatic psychological stress is a key risk factor for the development of various psychopathologies such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), resilience to stress appears to be the rule rather than the exception
We have shown that male Syrian hamsters who maintain social dominance for 2 weeks exhibit fewer negative behavioral (Morrison et al, 2014), neuroendocrine (Dulka et al, 2018b), and neurochemical (Dulka et al, 2017) consequences of social defeat stress compared to subordinates or controls
Given that acute stress-induced activation of serotonergic cells is positively correlated with stress susceptibility (Amat et al, 2005; Cooper et al, 2008, 2017; Paul et al, 2011), activation of ventromedial prefrontal cortex (vmPFC)-dorsal raphe nucleus (DRN) projections is thought to functionally suppress the DRN’s response during acute stress and buffer its negative consequences
Summary
While exposure to traumatic psychological stress is a key risk factor for the development of various psychopathologies such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), resilience to stress appears to be the rule rather than the exception. Accumulating evidence confirms that stress resilience can be learned, thereby implicating experience-dependent changes within the brain, which might be therapeutically recruited to promote resistance to stress-related impairments. This realization has encouraged numerous research efforts focused on elucidating the relationship between brain regions that underlie individual differences in stress processing, for example the ventromedial aspect of the prefrontal cortex (vmPFC) and the serotoninproducing, dorsal raphe nuclei (DRN). Several acutely administered traumatic stressors stimulate serotonergic activity within DRN, though in an opposing manner with activation correlating positively with stress susceptibility (Amat et al, 2005; Paul et al, 2011; Cooper et al, 2017). These findings indicate that an inverse relationship between vmPFC and DRN activity coincides with resistance to the adverse effects of acute traumatic stress
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