We found that mRNA expression of GABRA1, GABRG2, and GABRD was upregulated in iPSC-derived neural cultures following 21 days of exposure to 50 mM alcohol. Findings from previous studies using rodent in vitro and in vivo models to examine GABAA subunit expression following alcohol exposure have yielded variable results (for a detailed review, see (Grobin et al. 1998, Kumar et al. 2009). Variability in results may reflect differences in cell-type specific or brain-region specific regulation of gene expression in response to chronic alcohol exposure (Kumar et al. 2009). This work suggests that our results may only reflect transcriptional response in embryonic forebrain glutamatergic neurons. When considering inhibitory interneurons, a possibility arises that we did not observe robust changes in gene expression or electrophysiologic effects in response to prolonged alcohol exposure due to our cultures being enriched for excitatory glutamate neurons. While our electrophysiological recordings clearly demonstrate the presence of functional GABAA receptors, it may be that robust endogenous GABAergic synaptic transmission is needed during the alcohol exposure period to observe compensatory changes in expression and function. Utilizing a differentiation protocol
