A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression

Abstract

Modelling complex social behavior in the laboratory is challenging and requires analyses of dyadic interactions occurring over time in a physically and socially complex environment. In the current study, we approached the analyses of complex social interactions in group-housed male CD1 mice living in a large vivarium. Intensive observations of social interactions during a 3-week period indicated that male mice form a highly linear and steep dominance hierarchy that is maintained by fighting and chasing behaviors. Individual animals were classified as dominant, sub-dominant or subordinate according to their David's Scores and I& SI ranking. Using a novel dynamic temporal Glicko rating method, we ascertained that the dominance hierarchy was stable across time. Using social network analyses, we characterized the behavior of individuals within 66 unique relationships in the social group. We identified two individual network metrics, Kleinberg's Hub Centrality and Bonacich's Power Centrality, as accurate predictors of individual dominance and power. Comparing across behaviors, we establish that agonistic, grooming and sniffing social networks possess their own distinctive characteristics in terms of density, average path length, reciprocity out-degree centralization and out-closeness centralization. Though grooming ties between individuals were largely independent of other social networks, sniffing relationships were highly predictive of the directionality of agonistic relationships. Individual variation in dominance status was associated with brain gene expression, with more dominant individuals having higher levels of corticotropin releasing factor mRNA in the medial and central nuclei of the amygdala and the medial preoptic area of the hypothalamus, as well as higher levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor mRNA. This study demonstrates the potential and significance of combining complex social housing and intensive behavioral characterization of group-living animals with the utilization of novel statistical methods to further our understanding of the neurobiological basis of social behavior at the individual, relationship and group levels.

Fig 1. The mouse vivarium.

Fig 2. Frequency of observed social interactions.

a) Fighting, b) Chasing, c) All aggression, d) Sniffing, e) Grooming. Behaviors are directed from individuals in rows to those in columns.

Fig 3. Temporal changes in individual Glicko Dominance Ratings.

a) Fighting, b) Chasing, c) All aggression. All individuals arbitrarily begin with a 2200 rating and ratings are recalculated for each individual following a contest.

Fig 4. Visual representations of the a) fighting, b) chasing, c) sniffing and d) grooming social networks.

Nodes are colored from cream to red based on out-degree. More red colors represent individuals with a relatively higher out-degree. Fighting and chasing networks are based on the win-loss binary matrices. Sniffing and grooming networks are based on the presence-absence binary matrices.

Fig 5. Association between individual differences in Out-Closeness Centrality in the fighting network and relative gene expression.

a) CRF mRNA in the Medial Amygdala, b) CRF mRNA in the mPOA, c) GR mRNA in the hippocampus.