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Chunk #1 — Introduction

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μNeurocircuitry: Establishing models of neurocircuits with human neurons.
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Brain connections are complex, involving afferent and efferent processes from neurons residing in distinct brain areas forming an intricate neurocircuitry that governs behavior. For example, neurons located in the nucleus accumbens receive dopaminergic (DA) neuronal control from the midbrain and excitatory inputs from the prefrontal cortex, forming a circuitry that regulates motivation and reward1,2. Dysfunction of neural circuitry may result in neuropsychiatric disorders, including autism spectrum disorders (ASDs), schizophrenia and addiction. There are of en no effective therapies for these disorders, largely due to the lack of a mechanistic understanding of the pathophysiology. While animal models have provided significant insight into mechanisms underlying behavioral disorders, they may not capture the entire complexity of the human brain3. Furthermore, studies focused on the role of genetics and protein function may rely upon species differences that cannot be modelled in animals, unless the gene of interest is ectopically expressed4,5. Studies using human tissue have been limited, due both to scarce availability of suitable post-mortem or surgical tissues and the highly invasive tissue acquisition procedures. Ever since the discovery of the Yamanaka factors, iPSCs