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, males that were socially dominant prior to being placed into new social hierarchies 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 males who were socially subordinate prior to being placed into a new hierarchy. Specifically, the loss of social status in a new hierarchy (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, gaining social status in a new hierarchy (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 mu-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 these processes may support rapid social status changes.