While human-induced pluripotent stem cells (iPSCs) have been used to study different psychiatric disorders, in vitro models are of en limited to single-cell type analysis and mechanistic studies in a manner that does not account for circuit-level connections. Microfluidics have been used to create compartmentalized devices for neuronal cell culture for a variety of applications, including circuit studies, but have either been limited to primary cell sources or single-subtype human neurons. We demonstrate that we can generate excitatory, inhibitory and dopaminergic induced neurons (iNs) from human iPSC sources and these can recapitulate neuronal connections to form a multi-subtype μNeurocircuitry when cultured in our custom-designed culture devices. These human iNs possess neuronal morphology and display interchamber complex connectivity, as demonstrated here through morphological characterization and optogenetic manipulation. This novel μNeurocircuit can be used as a tool for studying human neuropsychiatric disorders, with a goal of providing a platform for developing novel therapies.
