Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety‐like behavior

Abstract

Social hierarchies are crucial for a group's survival and can influence the way an individual behaves and relates to a given social context. The study of social rank has been classically based on ethological and observational paradigms, but it recently has taken advantage of the use of other approaches, such as the tube test that measures territorial dominance without the display of in situ aggression and is executable in group‐living animals. However, little is known about how previous basal individual differences affect the development of dominance hierarchy measured in the tube test. We have analyzed in male mice body weight, locomotion, anxiety, and serum corticosterone both before and after the tube test, as well as adult hippocampal neurogenesis and transcriptome in the prefrontal cortex after the hierarchy had been established. We found differential gene expression between dominants and subordinates but no association between the other parameters and social status, neither pre‐ nor posttest. Our findings reveal that social rank in mice is stable along time and is not related to basal differences in stress, mood, or physical features. Lastly, real‐time quantitative PCR analysis confirmed differential expression of vomeronasal and olfactory receptors in the cerebral cortex between dominant and subordinate individuals, suggesting that differential brain gene expression in the medial prefrontal cortex could potentially be used as a biomarker of social dominance.—Pallé, A., Zorzo, C., Luskey, V. E., McGreevy, K. R., Fernandez, S., Trejo, J. L. Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety‐like behavior. FASEB J. 33, 6995–7008 (2019). http://www.fasebj.org

Gαi2+ vomeronasal neurons govern the initial outcome of an acute social competition

“…Other forms of dominance and aggression have also been reported to be mediated by distinct neural circuits (such as territorial vs infant-directed aggression 19,26 , or social status recognition vs dominance behavior 14 . In the present work, we have tried to correlate altered behavior in animals with impaired vomeronasal pheromone detection to a specific gene expression signature in the mPFC previously related to social dominance 20 . Vomeronasal function, specifically the Gαi2-expressing vomeronasal subsystem, may impact both instinctive and learned social responses that result in the establishment of hierarchies and the intensity of social interactions, mediated by interconnections between VNO epithelium, accessory olfactory bulb, medial amygdaloid complex, mPFC, and basolateral amygdala [27][28][29] .…”

“…Together, these Normal gene expression of markers related to dominance in a group-living social hierarchy for Gαi2-KO mutants. We have recently shown differential expression of a subset of 5 olfactory receptors and one V1R in the medial prefrontal cortex (mPFC) in group-living dominant vs. subordinate animals 20 . To test whether these genes are overexpressed in Gαi2 mutants, we performed real-time quantitative PCR in group-housed Gαi2 −/− mice and compared expression to group-housed controls, in both cases comprising dominant and non-dominant mice.…”

“…RNA extraction and reverse transcription assay. Total RNA extraction from medial prefrontal cortex samples and reverse transcription from RNA to cDNA was performed as described 20 .…”

“…Whether disruption of V1R pheromone detection and subsequent increase in male-male aggression have an influence in the establishment of social dominance remains unexplored. Further, we recently showed overexpression of a V1R gene and some olfactory receptor genes in the mPFC of dominant animals compared to subordinates 20 . These findings suggest a potential link between social hierarchy and vomeronasal function.…”

Sexually divergent effects of social dominance on chronic stress outcomes in mice

“…As a consequence, an individual's position in the dominance hierarchy has important consequences, including preferential access to food, shelter, and mates (13). Social rank within male hierarchies is also known to influence health, hormonal profile, brain function, metabolism and mortality (14,15). For instance, subordinate individuals display increased anxiety-like behavior, a suppressed immune response, higher basal corticosterone levels, and reduced life span (16).…”