Dr. Paola Arlotta has used human brain organoids—stem-cell-derived cell-culture models of human brain tissue—to show that when mutated, multiple genes associated with autism spectrum disorder (ASD) risk share an early developmental pattern in which inhibitory neurons develop out of step with the excitatory neurons they wire with. She hypothesizes this type of early asynchronous development of inhibitory neurons leads to later abnormalities in the activity and function of brain circuits, and that this mechanism may be shared across many ASD risk genes. This project seeks to directly test this hypothesis by examining circuit activity in human brain organoids mutant for the ASD risk gene ARID1b.