Neonatal Alcohol Exposure Induces Long-Lasting Impairment of Visual Cortical Plasticity in Ferrets

Abstract

Fetal alcohol syndrome is a major cause of learning and sensory deficits. These disabilities may result from disruption of neocortex development and plasticity. Alcohol exposure during the third trimester equivalent of human gestation may have especially severe and long-lasting consequences on learning and sensory processing, because this is when the functional properties and connectivity of neocortical neurons start to develop. To address this issue, we used the monocular deprivation model of neural plasticity, which shares many common mechanisms with learning. Ferrets were exposed to ethanol (3.5 mg/kg, i.p.) on alternate days for 3 weeks starting on postnatal day (P) 10. Animals were then monocularly deprived at the peak of ocular dominance plasticity after a prolonged alcohol-free period (15-20 d). Quantitative single-unit electrophysiology revealed that alcohol exposure disrupted ocular dominance plasticity while preserving robust visual responses. Moreover, optical imaging of intrinsic signals revealed that the reduction in visual cortex area driven by the deprived eye was much less pronounced in ethanol-treated than in control animals. Alcohol exposure starting at a later age (P20) did not disrupt ocular dominance plasticity, indicating that timing of exposure is crucial for the effects on visual plasticity. In conclusion, alcohol exposure during a brief period of development impairs ocular dominance plasticity at a later age. This model provides a novel approach to investigate the consequences of fetal alcohol exposure and should contribute to elucidate how alcohol disrupts neural plasticity.

Restoration of Neuronal Plasticity by a Phosphodiesterase Type 1 Inhibitor in a Model of Fetal Alcohol Exposure

“…every other day from postnatal day 10 (P10) until P30, which approximately mimics a binge-drinking episode once a week during the third trimester of gestation in humans. This alcohol exposure leads to ϳ250 mg/dl of blood alcohol concentration after the first 5 h and is undetectable after 34 h (Medina et al, 2003). Control littermates received saline solution or did not receive any treatment.…”

“…Optical imaging of intrinsic signals was performed with Imager 2001 VSDϩ (Optical Imaging System, Germantown, NY) by using imaging methods slightly modified from those described previously (Medina et al, 2003;Krahe et al, 2005). Briefly, animals were premedicated, anesthetized, and ventilated with similar procedures described for single-unit recordings.…”

“…There is growing evidence that abnormalities of cortical plasticity contribute to the cognitive deficits that characterize FAS (Rema and Ebner, 1999;Medina et al, 2003). However, the mechanisms by which prenatal alcohol exposure disrupts neocortical plasticity remain elusive.…”

“…Recently, we developed a ferret model of early alcohol exposure that provides a unique approach to unveil such mechanisms as well as to test different strategies to restore cortical plasticity. Animals exposed to alcohol during the third trimester equivalent of human gestation and monocularly deprived after a prolonged alcohol-free period are characterized by a permanent impairment of ocular dominance plasticity (Medina et al, 2003;Medina and Ramoa, 2005). Here, we try to restore ocular dominance plasticity in alcohol-exposed ferrets using the PDE type 1 inhibitor vinpocetine.…”

Antiepileptic drugs in women with epilepsy during pregnancy

“…There is also neuronal dysfunction found in the remaining neurons [Medina et al 2003]. These findings led to use of the apoptotic model in studies with AEDs.…”