No abstract

Prenatal infection increases risk for neurodevelopmental disorders such as autism in offspring. In the rodents, prenatal administration of the viral mimic Polyinosinic:polycytidylic acid (Poly I:C) allows for investigation of developmental consequences of gestational sickness on offspring social behavior and neural circuit function. Because maternal immune activation (MIA) disrupts cortical development and sociability, we examined social decision-making in a rat social affective preference (SAP) task. Following Poly I:C (0.5 mg/kg) on gestational day 12.5, male adult offspring (PN 50) exhibited atypical social interactions with stressed conspecifics whereas female SAP behavior was unaffected by maternal Poly I:C. Social responses to stressed conspecifics depend upon the insular cortex where corticotropin releasing factor (CRF) modulates synaptic transmission and SAP behavior. We characterized insular field excitatory postsynaptic potentials (fEPSP) in adult offspring of MIA or control treated dams. Male MIA offspring showed decreased sensitivity to CRF (300 nM) while female MIA offspring showed greater sensitivity to CRF compared to sham offspring. These sex specific effects appear to be behaviorally relevant as CRF injected into the insula of male and female rats prior to social exploration testing had no effect in MIA male offspring but increased social interaction in female MIA offspring. We examined the cellular distribution of CRF receptor mRNA but found no effect of maternal Poly I:C in the insula. Together these experiments reveal sex specific effects of prenatal infection on offspring social decision making and identify insular CRF signaling as a novel neurobiological substrate for autism risk.