a modest decrease observed for D40 AD-iNs (Supplemental Fig. S2D). The late effect of acute ethanol application displayed significantly different genotypic differences between N40 and D40 for sAP frequency (Supplemental Fig. S2D, *p ≤ 0.05). Furthermore, there was no difference observed in the amplitude of sAPs for both genotypes (Supplemental Fig. S2E). Only action potentials that displayed an overshoot were included for analysis. These data suggest that in response to ethanol application, AD-iNs containing MOR N40 variants display an enhanced release of GABA (Fig. 3), which increases the overall inhibitory tone. Since the AD-iNs generated are of the GABAergic variety, an increase of GABA release following ethanol application (Fig. 3) will activate GABAA receptors throughout the AD-iN population, thus ultimately shutting down neuronal excitability. These data further demonstrate that ethanol application causes a robust increase of GABA release, more prominently in iNs harboring the MOR major allele variant, N40, thus illustrating genotype-dependent sensitivity to acute ethanol application.
