DEVELOPMENTAL ETHANOL EXPOSURE IMPAIRS DENTATE GYRUS GABAERGIC INTERNEURONS

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Valenzuela CF1, Taylor DH1

1Department of Neurosciences and New Mexico Alcohol Research Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, U.S.A.

GABAergic interneurons regulate oscillatory network activity and information flow across the brain. Studies suggest that dysfunction of these cells is involved in the pathophysiology of several neurodevelopmental disorders. Several laboratories have documented alterations in interneuronal migration and function in animal models of fetal alcohol spectrum disorders. However, our understanding of the effects of ethanol on these specialized neurons is limited. In this study, we assessed the impact of ethanol exposure on developing dentate gyrus interneurons. We used transgenic mice in which GABAergic interneurons are tagged by expression of Venus fluorescent protein driven by the vesicular GABA transporter promoter (VGAT-Venus mice; generously provided by Dr. Yanagawa, Gunma University, Japan). Mice were exposed to ethanol using vapor inhalation chambers for 4 hr/day on gestational days 12-20 and postnatal days 2-9 (to model binge-like human exposure during the second and third trimesters of human pregnancy, respectively). Dentate gyrus GABA interneuron numbers were 8,173 ± 1,059 in controls and 4,644 ± 732 in ethanol treated samples at postnatal day 15 (p= 0.0337 n=4 pups from 4 different litters/group). We are currently investigating if specific interneuronal populations are affected by ethanol. Moreover, using slice electrophysiological techniques, we are characterizing the function of the surviving interneurons, as well as the effect of ethanol exposure on GABAergic transmission in dentate gyrus granule cells. Our findings suggest that developing GABAergic interneurons of the dentate gyrus are sensitive targets of developmental ethanol exposure. This work was supported by NIH grants R37-AA015614 and P50AA022534.

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