This study describes the development of a 3D microphysiological system that integrates functionally integrated glutamatergic and GABAergic neurons. The system involves the directed differentiation of human pluripotent stem cells (hPSCs) into subdomains of the forebrain, including the dorsal (pallium) and ventral (subpallium) forebrain, and their subsequent assembly to model the migration of interneurons into the cerebral cortex. The authors demonstrate that this system accurately recapitulates the saltatory migration of interneurons and their functional integration into cortical circuits. They also show that this approach can be used to model disease processes, such as Timothy syndrome, a neurodevelopmental disorder characterized by autism spectrum disorder and epilepsy, by examining the migration defects in interneurons derived from patients with the disease. The study highlights the potential of this 3D microphysiological system for studying the interaction of specific neuronal cell types and for generating personalized neural circuits in vitro.This study describes the development of a 3D microphysiological system that integrates functionally integrated glutamatergic and GABAergic neurons. The system involves the directed differentiation of human pluripotent stem cells (hPSCs) into subdomains of the forebrain, including the dorsal (pallium) and ventral (subpallium) forebrain, and their subsequent assembly to model the migration of interneurons into the cerebral cortex. The authors demonstrate that this system accurately recapitulates the saltatory migration of interneurons and their functional integration into cortical circuits. They also show that this approach can be used to model disease processes, such as Timothy syndrome, a neurodevelopmental disorder characterized by autism spectrum disorder and epilepsy, by examining the migration defects in interneurons derived from patients with the disease. The study highlights the potential of this 3D microphysiological system for studying the interaction of specific neuronal cell types and for generating personalized neural circuits in vitro.