Prenatal Ethanol Exposure Results in Cell Type, Age, and Sex-Dependent Differences in the Neonatal Striatum That...

Delayed motor development is an early clinical sign of fetal alcohol spectrum disorders. However, changes at the neural circuit level that underlie early motor differences are underexplored. The striatum, the principal input nucleus of the basal ganglia, plays an important role in motor learning in adult animals, and the maturation of the striatal circuit has been associated with the development of early motor behaviors. Here, we briefly exposed pregnant C57BL/6 dams to ethanol (5% w/w) in a liquid diet on embryonic days 13.5-16.5 and assessed the mouse progeny using a series of nine brief motor behavior tasks on postnatal days 2-14. Live brain slices were then obtained from behaviorally tested mice for whole-cell voltage- and current-clamp electrophysiology to assess GABAergic/glutamatergic synaptic activity and passive/active properties in two populations of striatal neurons: GABAergic interneurons and spiny striatal projection neurons. Electrophysiologically recorded spiny striatal projection neurons were also filled intracellularly with biocytin for post hoc analysis of dendritic morphology. We found that prenatal ethanol exposure resulted in developmental motor delays that were more severe in male mice and coincided with sex-dependent differences in the maturation of striatal neurons. Our findings indicate that prenatal ethanol exposure results in dynamic morphological and functional changes to the developmental trajectories of striatal neurons commensurate with the development of motor behaviors that differ between male and female mice.