Maternal-fetal interactions during the prenatal period are essential for brain development in the child. Maternal illness which increases the risk for neuropsychiatric disorders, including autism spectrum disorders (ASD), may impair these interactions. This grant will focus on developing and validating a new technology to examine the effects of alterations in materno-fetal interactions on fetal brain development. The researchers propose that the impact of maternal immune challenges and stressors on fetal brain development is a direct consequence of altered materno-fetal interactions taking place in the placenta. Circulating maternal tryptophan metabolism in the placenta is known to be required for protecting the fetus from maternal immunity. Preliminary results suggest that, during an early critical period of gestation, an alternative tryptophan pathway also provides serotonin to the fetal circulation and therefore may be critical for normal fetal brain wiring. A new model system will be used in mice to test the possibility that maternal immune challenges directly impact multiple placental metabolic pathways for tryptophan, disrupting fetal supply of serotonin and ultimately brain wiring in utero. This research provides unique opportunities to determine how maternally derived neurotransmitters, cytokines, hormones and drugs impact the development of brain circuits that have been implicated in autism spectrum disorders (ASD).