Individuals with autism spectrum disorder (ASD) exhibit high levels of behavioral inflexibility, characterized by “insistence on sameness” and restricted, repetitive patterns of behavior. This aspect of ASD is often debilitating for caregivers and affected individuals; however, it has been relatively underexplored in human and animal research. Recent neuropsychological studies suggest that the inflexible behavior observed in ASD individuals may result from impaired cognitive flexibility, defined as the ability to appropriately and efficiently adjust behavior in response to a changing environment.

Cognitive flexibility requires the proper functioning of basal ganglia circuits that are dynamically modulated by dopamine. Helen Bateup and her colleagues at the University of California, Berkeley, propose that synaptic alterations in the striatum, which is heavily influenced by dopamine and is the main input center of the basal ganglia, are central to cognitive inflexibility in ASD. Specifically, Bateup and her team hypothesize that changes in dorsal striatal circuits increase the propensity for motor habit formation, while impaired dopamine signaling results in inflexible decision-making strategies.

To test these ideas, Bateup’s team is using multiple genetic mouse models of ASD — SYNGAP1, CNTNAP2 and 16p11.2 deletion mice — to determine how ASD-risk mutations affect the cellular physiology and behavioral function of neurons comprising key striatal and dopaminergic circuits. Their work will also investigate whether distinct ASD-related genetic insults result in convergent cellular and behavioral phenotypes. Together, this work will advance our understanding of the synaptic mechanisms of habit learning and cognitive flexibility, and provide new insight into the neural basis of repetitive and restricted behaviors in ASD.