Affiliative behavioural phenotype and microglial activation predict social decision-making following immune activation

Social animals are faced with a critical decision when sick: to affiliate or withdraw. The behavioural response during an immune challenge varies by individual and species. However, the social and biological factors leading to variation in this decision during an immune challenge are unknown. Here, we explore the affiliative behavioural phenotype, “huddlers” and “non-huddlers,” as a social predictor, and microglial activation and peripheral cytokine expression as biological predictors of social-decision making during an immune challenge. To measure social-decision making, we recorded social approach and time spent in proximity to a familiar same-sex conspecific versus a novel object in the social California mouse following lipopolysaccharide (LPS) treatment. Behavioural phenotype predicted both the social response to LPS and the relationship between cytokine activity and social behaviour, suggesting that social experience regulates social decision-making during sick versus healthy conditions. Additionally, we found that elevated microglia activity in the dentate gyrus (DG) and medial prefrontal cortex (mPFC) negatively correlated with social behaviour, positioning these regions for future exploration for the role of microglia on social decision-making. Our results identify the predictive power of behavioural phenotypes on social response to sickness and a link between microglia and decision-making during sickness.