though actions on metabotropic glutamate and GABAB receptors (Nie et al. 2000, Zhu and Lovinger 2006). By exogenously applying GABA to evoke a current, we could examine only postsynaptic GABAA receptor function. Future studies using iPSC-derived neurons could extend our findings by examining the effects of alcohol on endogenous inhibitory synaptic transmission, including the frequency and amplitude of spontaneous inhibitory currents. Using drugs targeting presynaptic metabotropic GABAB receptors in conjunction with alcohol could aid in differentiating presynaptic from postsynaptic effects of alcohol in this model system. Although our method of puff-application of GABA to evoke a postsynaptic current targeted primarily somatic GABAA receptors, rodent models suggest that alcohol effects are greater on the potentiation of GABAA receptors located on the soma and proximal vs. distal dendrites (Weiner et al. 1997, Wu et al. 2005). Although these finding suggest that somatic and proximal GABAA receptors are more sensitive to the effects of alcohol, it remains to be determined whether these findings translate into human iPSC-derived neurons. Future studies could examine the possible sub-localization of more alcohol-sensitive GABAA receptors by focal puff application of GABA onto different regions of the neuron.
