Kcnn2 blockade reverses learning deficits in the mouse model of Fetal Alcohol Spectrum Disorders

Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. Those include Fetal Alcohol Spectrum Disorders (FASD) with a wide range of cognitive deficiencies including impaired motor skill development. While these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We have previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells alter gene expression in their descendant neurons. Among the altered genes, an increase of the calcium-activated potassium channel Kcnn2 in the motor cortex correlates with motor learning deficits in the mouse model of FASD. Pharmacologic blockade of Kcnn2 improves these learning deficits, suggesting Kcnn2 blockers as a novel intervention for learning disabilities in FASD.