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Chunk #30 — Discussion — Compartmentalized cultures as models for neurocircuitry

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μNeurocircuitry: Establishing models of neurocircuits with human neurons.
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In neuropsychiatric disorder research, animal models have provided much insight into affected pathways; however there are certain aspects of human specific pathophysiology that cannot be recapitulated by animal models4,5. Recent developments in stem cell biology enable the study of the pathophysiology of neuropsychiatric disorders using human neurons; however, the human neurons are of en cultured in a 2D, single-chamber configuration. Synaptic connections between neurons in these cultures are apparently random. In pursuit of in vitro circuit-level models, researchers have taken advantage of soft lithography techniques to generate microdevices for synaptic communication. Previous studies have successfully demonstrated compartmentalized primary neuronal cultures for a variety of applications22,23. They have also demonstrated the use of calcium imaging and optogenetics as tools for investigating communication between chambers21. Here, we have extended this work by seeding human neuronal cells into a custom-designed compartmentalized device which can mimic one group of neurons receiving 2–4 different types of inputs. Different subtypes of human iNs survive in co-culture conditions within the device through 4 weeks and are primarily maintained within their respective compartments, while communicating to the central