the patient iN cells, but also revealed that the N40D SNP mediates a more robust decrease in excitability and synaptic release, which was accompanied with disruption of a putative N-linked glycosylation motif observed in human D40 MOR 34. The MOR is a GPCR and its activation has been shown to impact calcium as well as potassium influx in neurons 35, both processes affect the calcium dependency of synaptic vesicle release. The primary effect of MOR activation is a dampening in neuronal excitability. The A118G SNP does not affect baseline synaptic function per se, which can be seen based on our comparison of baseline sIPSC responses in N40 and D40 neurons (sIPSCs, Figs.1&2). However, it does affect the response of iN cells to MOR agonists (DAMGO and morphine). Based on the results of our study, the N40D SNP causes a more robust suppression of neuronal excitability upon MOR activation by DAMGO and also causes a stronger suppression of synaptic release. These data will help to elucidate the synaptic consequences of the N40D SNP in human neurons.
