We focused the remaining analyses on one pair of isogenic cell lines, C12 (D40) and A10 (N40), on the basis of their consistent differentiation and maturation. We found that DAMGO application more robustly decreased mIPSC frequency in D40 versus N40 iN cells, which no change in mIPSC amplitude (Fig. 3A–C), which suggests a DAMGO mediated decrease in synaptic release. Consistent with the decrease in mIPSC frequency, we observed that DAMGO decreased evoked IPSC amplitude more robustly in D40 iN cells compared to N40 iNs (Fig. 3D–E). This is consistent with the hypothesis that MOR activation by DAMGO in human iN cells more robustly decreases neurotransmitter release probability in D40 iN cells compared to N40 iN cells, suggesting that the A118G SNP directly regulates synaptic function.
