Effect of Enriched Environment Rearing on Impairments in Cortical Excitability and Plasticity after Prenatal Alcohol Exposure

Abstract

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.

Theory for normal and impaired experience-dependent plasticity in neocortex of adult rats

“…(iii) The short latency (Ͻ10 ms poststimulus), presumably thalamocortical (TC) components of responses were also subject to change. In the normal cortex, the short latency component elevated over days (4), whereas in the impaired cortex it decreased (12).…”

“…1a). To alter the pattern of sensory activity, all whiskers except two were cut close to the fur on one side of the face (12). The principal whisker D2 and one adjacent (surround) whisker in the D row (i.e., D1) were spared.…”

“…After measured time intervals up to 30 days of whisker pairing (whiskers were reclipped regularly), the activity of single neurons in the D2 barrel-column was measured in response to controlled mechanical deflections of the principal D2 whisker, the intact ''Dpaired'' surround whisker (D1), and three surrounding cut neighbors (''D-cut'' ϭ D3, C2, and E2). The same electrophysiological measurements were performed in the barrel cortex of normal adult rats and adult rats that were prenatally exposed to alcohol (PAE rats) (12). Pregnant dams consumed 6.5% ethanol in a nutritionally complete liquid diet during the whole period of pregnancy.…”

“…Whisker pairing had caused plastic neural changes in both the control adult cortex and the PAE adult cortex. However, the nature of the changes differed markedly (12). (i) Neurons in the normal barrel-column showed potentiation of responses to deflections of spared whiskers in less than 1 day of whisker pairing (5), whereas these responses in the barrel-column of PAE rats required at least 14 days to reach statistically significant elevation compared with pre-whiskerpairing values (12).…”

“…However, the nature of the changes differed markedly (12). (i) Neurons in the normal barrel-column showed potentiation of responses to deflections of spared whiskers in less than 1 day of whisker pairing (5), whereas these responses in the barrel-column of PAE rats required at least 14 days to reach statistically significant elevation compared with pre-whiskerpairing values (12). Most of the response changes occurred in the long latency (10-100 ms poststimulus) response components thought to be mediated by intracortical connections.…”