Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress

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...

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Bibliographic Details
Published in:	Frontiers in neural circuits Vol. 14; p. 50
Main Authors:	Grizzell, J. Alex, Clarity, Thomas T., Graham, Nate B., Dulka, Brooke N., Cooper, Matthew A.
Format:	Journal Article
Language:	English
Published:	Lausanne Frontiers Research Foundation 16-10-2020 Frontiers Media S.A
Subjects:	acute stress Behavior Cholera toxin Cholera toxin B subunit dominance Dominance hierarchies Dorsal raphe nucleus Hindbrain Laboratory animals Neurons Neuroscience Post traumatic stress disorder Prefrontal cortex raphe Raphe nuclei resilience social defeat Social interactions Subordinates Surgery
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Summary:	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 subordinates and become stress-vulnerable following pharmacological inhibition of the vmPFC. Dominants also display fewer stress-activated DRN neurons than subordinates, 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Aras Petrulis, Georgia State University, United States; Kechun Yang, University of Pennsylvania, United States Edited by: Fu-Ming Zhou, The University of Tennessee Health Science Center, United States
ISSN:	1662-5110 1662-5110
DOI:	10.3389/fncir.2020.00050