To further verify our findings on the deficit in development of hippocampal granule neurons carrying the SCZD genetic background, we investigated the synaptic function of the hiPSC-derived PROX1+ neurons that were differentiated for at least 4 weeks in culture on hippocampal astrocytes using whole-cell patch-clamp recordings. To specifically assess the hippocampal granule neurons, cells indicated by a lentiviral PROX1-EGFP reporter construct were selected for recording (Figures 7A and 7B; Figure S1 available online). Similar to the control hiPSC-derived neurons, the SCZD PROX1+ neurons showed normal levels of transient sodium inward currents and sustained potassium outward currents evoked by voltage step depolarization (Figures 1C and 7D), and they were able to fire action potentials in response to somatic current injection (Figures 7E and 7F). These observations indicated that the PROX1+ granule cells derived from the SCZD hiPSCs lines showed functional features of neurons. Interestingly, quantitative measurements of spontaneous neurotransmitter release revealed a significant decrease in the frequency of the spontaneous ESPCs (sEPSCs) in the SCZD neural network (Figure 7H; 0.76 ± 0.14 Hz, n = 42, p < 0.003) compared to
