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Chunk #36 — Discussion

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Examining the effects of alcohol on GABA receptor mRNA expression and function in neural cultures generated from control and alcohol dependent donor induced pluripotent stem cells.
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Furthermore, based on our current experimental methods it is not possible to easily relate changes observed in gene expression following alcohol to functional adaptations that may relate to the development of tolerance. Due to the extensive recording time required for whole cell patch clamp electrophysiology we needed to examine cells over a range of alcohol exposure lengths (9–21 days) in order to accumulate sufficient number of cell recordings for each neural cell line. Cells used for electrophysiological analysis were also maintained longer in culture prior to alcohol exposure to enhance the maturation of neuronal properties (Fink et al. 2017). Whether molecular adaptations in control and alcoholic-derived neurons lead to functional electrophysiological differences might be better examined by use of GABAA subunit-selective agonists and antagonists during electrophysiology recordings following chronic alcohol exposure, such as the GABAA δ-subunit-preferring agonist gaboxadol (THIP) (Chandra et al. 2010, Diaz et al. 2014).