Maternal infection is an environmental factor that can increase the incidence of autism in the offspring. In an animal model of this risk factor, respiratory infection of pregnant mice yields offspring that develop behavioral abnormalities and neuropathology consistent with those observed in autistic patients. These changes can be mimicked by maternal injection of the dsRNA, poly(I:C), which evokes an anti-viral inflammatory response. Recent studies have shown that the cytokine interleukin-6 (IL-6) is necessary and sufficient for mediating the development of behavioral and transcriptional changes in this maternal immune activation (MIA) model. While IL-6 is critical for mediating the effects of MIA, the mechanism by which IL-6 acts to alter neural development is unknown. Preliminary results indicate that IL-6 activates cells in the placenta and fetal brain, causing the induction of IL-6 response genes and IL-6 mRNA as well. This project will identify the cells that respond to IL-6 and localize the source(s) of IL-6 production. The long-term goals are to elucidate the molecular mechanisms by which IL-6 alters fetal brain development and to discover how these defects influence postnatal behavioral dysfunction.