aspects that may have led to this pathophysiology. Moreover, transgenic animal models can only reproduce some attributes of SCZD and cannot fully recapitulate the key genetic events associated with the pathogenesis of the disease. Using our differentiation approach, we generated hippocampal granule neurons from hiPSC lines previously derived from the fibroblasts of four control and four schizophrenic individuals (Brennand et al., 2011). We first “prepatterned’ the previously derived hiPSCs to DG precursors and then, using our in vitro model of hippocampal neurogenesis, found that whereas SCZD hiPSCs gave rise to a NPC population with similar levels of PAX6 and EMX2 as controls, they had reduced levels of PROX1 and NEUROD1, suggesting deficits in generating hippocampal granule neurons from the neural progenitor pool. Strikingly, functional characterization of neural networks of SCZD and control neurons using calcium imaging showed a significant reduction in the percentage of active neurons. Further investigation by electrophysiological recording of hiPSC-derived, Prox1+ neurons revealed that whereas both SCZD and control neurons displayed similar basic neuronal characteristics of Na+/K+ currents and evoked action potentials, SCZD neurons exhibited reduced levels of spontaneous neurotransmitter release, which may be associated with a less mature state of the neurons. Our work provides additional
