Prenatal immune challenge compromises development of upper-layer but not deeper-layer neurons of the mouse cerebral cortex.

Maternal infection during pregnancy is an environmental risk factor for the offspring to develop severe brain disorders, including schizophrenia. However, little is known about the neurodevelopmental mechanisms underlying the association between prenatal exposure to infection and emergence of cognitive and behavioral dysfunctions later in life. By injecting the viral mimetic polyriboinosinic-polyribocytidylic acid (Poly I:C) into mice, we investigated the influence of maternal immune challenge during pregnancy on the development of the cerebral cortex, a responsive organ for cognition. Stimulation of the maternal immune system did not influence the cell number or density of the cortical neurons of postnatal 10-day-old and 8-week-old offspring, whereas gene expressions of upper-layer-specific transcription factors were significantly reduced, without affecting those of the deeper-layer ones. Moreover, the prenatal Poly I:C injection impaired synaptic development of the upper-layer neurons at a later stage, and there was a decrease in the synaptophysin- and glutamic acid decarboxylase-67-positive puncta surrounding the neuronal cell bodies and an increase in the dendritic spine density in postnatal 8-week-old offspring. Considering their importance for cognitive function, the specific abnormalities in the development of upper-layer neuronal phenotypes may underlie the development of psychiatric brain and behavioral dysfunctions emerging after in utero exposure to an infection.