To determine whether the increased sensitivity of D40 iN cells is a DAMGO-specific effect or whether it can be observed across other MOR-specific agonists, we studied the effect of morphine in modulating synaptic release in both N40 and D40 iN cells. In response to 100 ¼M morphine, we observed a robust suppression of both sIPSC frequency and amplitude in both N40 and D40 iN cells with a significantly stronger sIPSC suppression in D40 iN cells compared to N40 iN cells (Supplemental Fig. 6). We also performed morphine wash out experiments to demonstrate that sIPSC suppression was reversible (Supplemental Fig. 6). These data substantiate the D40-specific increased sensitivity observed in human iN cells.
