Neurobiological mechanisms of autism - associated aggression

The project aims to identify neurobiological underpinnings of autism spectrum disorder (ASD)-associated aggression. Two out ofthree individuals with autism exhibit aggression - behaviour with highly detrimental effects on the affected individual's life. Predictors of aggression in typically developing individuals (e.g. gender, age, socioeconomic status) are not associated with ASD-related aggression, suggesting that different mechanism(s)/aetiology are driving the aggression in ASD. Previously, we have identified two animal models of ASD (i.e. Nlgn3 knock-in (KI)and Nrxn1a knock-out (KO) mice) which, in addition to a strong construct and face validity for ASD, also present with a robust aggressive phenotype. In this project, we will use state-of-the-art technologies, including the optogenetic fMRI, to establish causal relationships between genetic mutations in Nlgn3 and Nrxn1a (two of the most frequent mutations in humans with autism) and observed aggression, as well as to identify potential pharmacological treatments