Systematic analysis of synaptic dysfunction in neuropsychiatric disorders using human pluripotent stem cell derived neurons

The precise cellular and molecular mechanisms governing complex neuropsychiatric disorders, such as autism spectrum disorders, intellectual disability, and schizophrenia remain unclear. Multiple studies of patient genomes indicate that specific mutations in genes involved in the development and function of synapses are repeatedly observed in patients with these disorders, suggesting that synaptic dysfunction potentially serves as a common pathological mechanism. In this seminar, I will address our recent efforts in developing and applying genetic and cellular tools from human pluripotent stem cells to better model neuropsychiatric disease-relevant phenotypes and mechanisms. Specifically, I will use neurexin 1 (NRXN1) mutation as an example whereby a systematic analysis of this high-risk allele has revealed synaptic phenotypes relevant to schizophrenia.