It has been shown that activation of MOR signaling causes suppression of inhibitory neurons which finally leads to excitation of midbrain dopaminergic (DA) neurons, a disinhibition mechanism 31, 32. We therefore derived inhibitory induced neuronal (iN) cells from all 7 iPS cell lines by lentiviral mediated ectopic expression of the transcription factors Ascl1 and Dlx2 27. These induced human neuronal cells express pan-neuronal markers including MAP2, βIII-tubulin, and Synapsin (Fig. 1C, Supplemental Fig. 1B) as well as inhibitory neuronal markers GAD67 and VGAT (Fig. 1D, Supplemental Figs. 1C, 1N–O). They also exhibit OPRM1 of similar expression levels (Supplemental Fig. 1M). Thus, the N40D SNP has no impact on MOR expression or inhibitory neuronal identity. To examine whether the N40 and D40 iN cells are functionally comparable under baseline conditions, we performed whole cell patch-clamp recordings of iN cells after 5-6 weeks of re-plating onto a monolayer of mouse glia. The iN cells of both genotypes exhibit similar intrinsic membrane properties (Supplemental Fig. 1D–F), can fire repetitive spontaneous action potentials (APs) at baseline levels (Supplemental Fig. 1G–I), and exhibit similar intrinsic
