Investigating the Role of Androgen Receptor Expression in the Ventral Premammillary Nucleus for Hierarchy Maintenance

Abstract

In many species that exhibit social behavior, individuals develop dominance hierarchies and occupy different social ranks. An individual’s rank is often flexible and dictates their access to resources (Wang et al., 2014). One way that social hierarchy manifests itself in humans is through socioeconomic status (SES), which has been linked to negative health outcomes like increased mortality and higher rates of disease (Wang et al., 2014; Demakakos et al., 2008; Sapolsky 2005). The neural mechanism that modulates social rank remains unknown, and its discovery could have important implications for treatment of SES-related health issues. Mice are a common model system used to study hierarchies, as they develop linear and stable dominance hierarchies (Wang et al., 2014). Within the mouse brain, the ventral premammillary nucleus (PMv) is thought to play an essential role in goal-oriented aggression and hierarchy behaviors (Falkner & Lin, 2014; van den Berg et al., 1983; Stagkourakis et al., 2018; Soden et al., 2016). Androgen receptors (ARs) have also proven to be important for aggressive behaviors and are densely expressed in the PMv (Cunningham et al., 2012; Simerly et al., 1990; Wood & Newman, 1999). Thus, the expression of ARs in the PMv may act as a mechanism for the stabilization and flexibility of rank-related behaviors, specifically ones that require chemosensory detection. The goal of the current research is twofold: (1) to characterize and compare dominance behaviors in males and female mice and (2) to test whether AR expression in the PMv is necessary to maintain hierarchies. To achieve the first goal, group social rank and behavior was assessed using a direct competition assay and a resource foraging assay. Males and females tended to display similar behavioral strategies to establish dominance in these assays. To explore the second goal, social hierarchies were assessed with a direct competition assay. Then, AR expression in the PMv was virally ablated and the same hierarchies were reassessed to determine whether the ablation affected hierarchy stability. The ablation of AR expression in the PMv did not appear to significantly affect hierarchy stability or the use of dominance behaviors. However, it did significantly increase the amount of time it took for a winner to be established in the direct competition assay. Taken together, these experiments provide insight into how hierarchy and social rank are modulated within the brain. This research also allows us to explore sex differences in the expression and maintenance of dominance behaviors, which is important because female hierarchies are currently understudied.