Abnormal reinforcement learning in a mice model of autism induced by prenatal exposure to valproic acid.

Abstract Individuals with autism spectrum disorder (ASD) display dysfunction in learning from environmental stimulus that have positive or negative emotional values, posing obstacles to their everyday life. Unfortunately, mechanisms of the dysfunction are still unclear. Although early intervention for ASD victims based on reinforcement learning are commonly used, the mechanisms and characteristics of the improvement are also unknown. By using a mice model of ASD produced by prenatal exposure to valproic acid (VPA), the present work discovered a delayed response-reinforcer forming, and an impaired habit forming in a negative reinforcement learning paradigm in VPA exposure male offspring. But the extinction of the learned skills was found to become faster than normal male animals. Since escape action of nosepoking and the motility remain unchanged in the VPA male offspring, the impaired learning and the accelerated extinction are caused by deficits in higher brain functions underlying association between the animals’ behavioral responses and the outcomes of such responses. The results further suggest that the rodent ASD model produced by prenatal exposure to VPA reproduces the deficits in reasoning or building the contingency between one’s own behaviors and the consequent outcomes of the behavior seen in ASD patients.