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 evidence that hippocampal neurogenesis is compromised in SCZD patients and supports the hypothesis of an immature DG in patients with SCZD. Moreover, our findings suggest that the deficit may originate in the development of the NPCs into the DG granule neurons and that the delayed maturation of SCZD DG granule neurons resulted in attenuation of functional network connectivity and activity levels in the SCZD hiPSC-derived neurons, potentially producing a non-cell-autonomous defect in the property of the hippocampal neural circuitry. Our previous study using microarray gene expression analysis indicated a deficiency in the number of cellular pathways in these SCZD hiPSC-derived neurons, including in the canonical WNT/β-catenin pathway (Brennand et al. 2011). Because our differentiation approach utilizes Wnt3a to mimic conditions in the developing DG, it is conceivable that deficits observed in the SCZD neurons may be due to altered levels of WNT signaling. However, additional work is needed to verify this possibility and elucidate mechanisms that attribute to this defect.
