Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies

Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies. We show that mice of all social ranks rapidly establish new stable social hierarchies when placed in novel social groups with animals of equivalent social status. Seventy minutes following social hierarchy formation, previously socially dominant animals exhibit higher increases in plasma corticosterone and vastly greater transcriptional changes in the medial amygdala (MeA), which is central to the regulation of social behavior, compared to previously subordinate animals. Specifically, social descent is associated with reductions in MeA expression of myelination and oligodendrocyte differentiation genes. Maintaining high social status is associated with high expression of genes related to cholinergic signaling in the MeA. Conversely, social ascent is related to relatively few unique rapid changes in the MeA. We also identify novel genes associated with social transition that show common changes in expression when animals undergo either social descent or social ascent compared to maintaining their status. Two genes, Myosin binding protein C1 ( Mybpc1 ) and μ-Crystallin ( Crym ), associated with vasoactive intestinal polypeptide (VIP) and thyroid hormone pathways respectively, are highly upregulated in socially transitioning individuals. Further, increases in genes associated with synaptic plasticity, excitatory glutamatergic signaling and learning and memory pathways were observed in transitioning animals suggesting that adaptations in these processes may support rapid social status changes. Author Summary We investigate how male CD-1 mice behaviorally, physiologically, and molecularly respond to changes in their social hierarchies. We found that mice rapidly reform social hierarchies when placed into novel social groups. Formerly dominant mice experience the greatest increase in stress hormone levels and the largest shifts in gene expression in the medial amygdala, a brain region crucial for regulating social behavior. Specifically, we observed reduced expression of genes related to myelin production and maintenance as well as cholinergic functioning in formerly dominant males who socially descended. In contrast, formerly subordinate males who socially ascended displayed fewer genomic changes. Moreover, we identified a set of genes that change expression when animals transition their social status regardless of whether they rise or fall in rank. These social transition genes provide new insights into the biological mechanisms underpinning social plasticity. Our findings demonstrate the distinct molecular mechanisms that are shared between socially ascending versus descending mice, as well as those that are unique to each type of social transition. ### Competing Interest Statement The authors have declared no competing interest.