The formation of the human cerebral cortex involves the assembly of circuits composed of glutamatergic neurons, which are generated in the dorsal forebrain (pallium), and GABAergic interneurons, which are born in the ventral forebrain (subpallium)1–3. After specification, interneurons migrate long distances over several months during human fetal development and subsequently undergo activity-dependent maturation and integration into cortical circuits1,4. Genetic or environmental perturbations of this process can lead to an imbalance of cortical excitation and inhibition and are thought to contribute to neuropsychiatric disorders, including epilepsy and autism spectrum disorders (ASD)5,6. These key developmental processes, which occur mostly in mid-to-late gestation, have been largely inaccessible for functional studies in humans7,8. Moreover, the directed differentiation, and particularly the functional maturation of cortical interneurons from human pluripotent stem cells (induced pluripotent stem cells, hiPSC, or embryonic stem cells, hESCs), has been challenging9,10. To date, no reliable, personalized models exist to study the migration of human interneurons and their functional integration into cortical ensembles.
