Abstract # 3153 Microglial phagocytosis of newborn cells is induced by endocannabinoids and sculpts sex differences in social play

The amygdala is a sexually dimorphic brain region important for juvenile social play behavior. During neonatal development, the male amygdala contains fewer newborn cells than females. This sex difference inversely correlates to the expression of juvenile social play, a process we previously demonstrated to be the result of a higher developmental endocannabinoid (ECB) tone in the male amygdala. We now report that microglia, the resident immune cells of the brain, are more phagocytic in the male amygdala during this postnatal window, suggesting a possible mechanism by which ECBs affect the number of newborn cells. Based on these data, we hypothesized that microglia control the number of newborn cells in the postnatal rat amygdala by phagoptosing (targeted phagocytosis of viable cells) newborn cells in an ECB-dependent manner. Administering testosterone or cannabinoid receptor agonists to female pups masculinized the number of phagocytic microglia and correspondingly decreased the number of newborn cells. Further analysis found that microglia engulf newborn cells, and in males, microglia phagocytose more newborn astrocytes. Inhibiting phagocytosis increased the number of newborn cells only in males, demonstrating that newborn cells can survive if phagocytic activity is prevented. Together, these data suggest that sex differences in the local environment of the developing amygdala instruct microglia to actively phagoptose newborn cells as a means to sculpt the later life architecture of the amygdala .