Project 462646

Difficulties in social interactions is a core behavioural symptom of autism spectrum disorder(ASD). Over the last decade, many ASD-linked gene mutations have been identified; however, how these gene mutations lead to a common set of brain abnormalities that cause the social impairments associated with ASD is not well understood. To study this, we will perform behavioural and imaging experiments with three lines of genetically engineered mouse models with targeted disruptions of distinct ASD-risk genes. In each mutant mouse line, we will examine activity patterns of the brain network governing social behaviour and identify how they are different from normal mice and between different mutant mouse lines. Then, we will focus on a specific brain area called the nucleus accumbens, a key hub of the brain's social network and proposed site for oxytocin's pro-social effects. We will examine whether any or all of the three models exhibit abnormal regional activity during social behaviour, and if oxytocin application normalizes it. Results obtained from this study will help identifying overlapping neural mechanisms of social dysfunction across multiple ASD gene mutations, and thus improve our understanding of disorder etiology and suggest novel treatment targets.