Building on these previous approaches, we have developed a μNeurocircuitry model of neurons capable of receiving multiple inputs, which allows the study of a simplified version of human brain circuitry, with a goal of elucidating neuropsychiatric disorder pathology. We have developed a five-compartment neurocircuit model fulfilling the following requirements: 1) chemically distinct compartmentalization with microchannels, enabling defined synaptic connections, 2) a large, open central chamber, allowing spatial access for patch clamp apparatus and 3) feasibility for the culture of human-derived neurons to model the human-specific aspects of these disorders. We have used iN cell technology to generate excitatory (glutamatergic), DA and inhibitory (GABAergic) subtype human neurons from patient-specific iPSC sources. We demonstrate that these neurons express subtype-specific markers and develop functional synaptic connections between the outer and central culture chambers. We anticipate that this device will be useful for the study of brain circuits between various neuronal subtypes as they relate to neuropsychiatric disorders.
