Effect of enriched environment rearing on impairments in cortical excitability and plasticity after prenatal alcohol exposure.

The daily ingestion of alcohol by pregnant mammals exposes the fetal brain to varying levels of alcohol through the placental circulation. Here we focus on the lingering impact on cortical function of 6.5% alcohol administered in a liquid diet to pregnant rats throughout gestation, followed by 3 alcohol-free months before brain function was analyzed in the offspring. Both spontaneous activity of the neurons in the barrel cortex and the level of response to test stimuli applied to the whiskers remained reduced by >75% after alcohol exposure. Whisker pairing, a type of cortical plasticity induced by trimming all but two whiskers in adult rats, occurred in <1 d in controls, but required 14 d to reach significance after alcohol exposure. These long-term neuronal deficits are present in all layers of cortex and affect neurons with both fast and slow action potentials. Plasticity is first seen in the total sample of neurons at 14 d; however, by 7 d, neurons in layer II/III already show plasticity, with no change in layer IV neurons, and a reverse shift occurs toward the inactive whisker in layer V neurons. Analysis of NMDA receptor subunits shows a persistent, approximately 30-50% reduction of NR1, NR2A, and NR2B subunits at postnatal day 90 in the barrel field cortex. Exposing the prenatal alcohol-exposed rats to enriched rearing conditions significantly improves all measured cortical functions but does not restore normal values. The results predict that combinations of interventions will be necessary to completely restore cortical function after exposure of the fetal brain to alcohol.