There is increasing evidence that maternal infection in humans is associated with placental dysfunction and an increased risk for autism in the offspring. In animal models, maternal infection causes behavioral and molecular changes in the offspring that are consistent with those seen in autism. However, the mechanisms by which infection, leading to maternal immune activation, alters fetal brain development are poorly understood. The goal of this project is to characterize the impact of maternal infection and immune activation during pregnancy on placental function, and the downstream consequences on fetal brain development. We recently discovered that the placenta, which is a major interface between mother and fetus, converts maternal tryptophan to serotonin during early pregnancy, thereby providing a source of serotonin for the developing fetal brain. Furthermore, dysregulation of serotonin levels in the developing fetal brain has been associated with the onset of autism spectrum disorders in the offspring. Disruption of this placental tryptophan metabolism during pregnancy may constitute a molecular mechanism by which maternal immune activation contributes to the later onset of disorders like autism in the offspring. Through the use of our novel ex vivo placental perfusion system, we will test the hypothesis that maternal immune activation directly alters placental tryptophan metabolism, ultimately affecting fetal brain development, and contributing to the onset of autism spectrum disorders.