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Chunk #29 — Discussion

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μNeurocircuitry: Establishing models of neurocircuits with human neurons.
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To harness the power of patient-specific neuronal cells for studying neuropsychiatric disorders, we created a simple and scalable system that can mimic the intricately connected neuronal circuitry in the brain. In this study, we have developed a five-compartment μNeurocircuit model, where a population of neurons analogous to the mid-brain region receives input from at least two different populations. The system allows the use of functional assays such as synaptic physiology combined with optogenetic activation of a specifc neuronal pathway. Our results validate this device as a unique tool for dissecting the complex mechanisms underlying neuropsychiatric disorders. Through morphological as well as functional analysis, we have the capacity to investigate various functional/morphological disease phenotypes found in psychiatric disorders (e.g. altered dendritic branching, synapse number and altered synaptic potentiation), while accounting for the role of upstream neurons in circuit with their synaptic targets.