Emerging roles for microglia and microbiota in the development of social circuits

Social withdrawal is a core component of the behavioral response to infection. This fact points to a deep evolutionary and biologic relationship between the immune system and the social brain. Indeed, a large body of literature supports such an intimate connection. In particular, immune activation during the perinatal period has been shown to have long-lasting consequences for social behavior, but the neuroimmune mechanisms by which this occurs are only partially understood. Microglia, the resident immune cells of the brain, influence the formation of neural circuits by phagocytosing synaptic and cellular elements, as well as by releasing chemokines and cytokines. Intriguingly, microbiota, especially those that reside within the gut, may also influence brain development via the release of metabolites that travel to the brain, by influencing vagal nerve signaling, or by modulating the host immune system. Here, I will review the work suggesting important roles for microglia and microbiota in social circuit formation during development. I will then highlight avenues for future work in this area, as well as technological advances that extend our capacity to ask mechanistic questions about the relationships between microglia, microbiota, and the social brain.