In this paper, we have demonstrated the proof-of-principle use of soft lithography to generate a compartmentalized system for modeling human brain neurocircuits. Subtype specific human iNs are cultured within individual, interconnected chambers and recapitulate defined synaptic connections. This system not only can specify neuronal dysfunction at a circuitry level but has the capability to capture human-specific elements of disorders (e.g. single-nucleotide polymorphisms only present in human neurons). Using this system, we can monitor circuit-level changes unique to the patient's genetic background with a goal of drug screening for personalized medicine which operates at the neurocircuitry level. We expect that this approach will enable more accurate in vitro models of neuropsychiatric disorders and that it will facilitate translation of drug candidates into clinical trials.
