Effects of Early Alcohol Exposure on Ocular Dominance Plasticity

Fetal alcohol spectrum disorder is the leading cause of mental retardation in the western world. It is associated with learning and sensory deficits. Some of these deficits are a result of faulty neuronal plasticity. Previously our lab has used ferrets to demonstrate that alcohol exposure during the third trimester of human gestation results in impaired ocular dominance plasticity (ODP). Here we have transferred this model to mice. Mice, treated with 5 mg/kg of ethanol on postnatal days 5, 7 and 9, exhibit a lack of ODP plasticity after 10 days of monocular deprivation (MD) during the critical period of visual cortex plasticity, as seen by optical imaging of intrinsic signals. This deficit in ODP was rescued by treatment with a phosphodiesterase type 1 inhibitor (PDEi1), vinpocetine. This rescue did not occur after treatment with a PDEi4 (rolipram) or a PDEi5 (vardenafil) inhibitor alone. Interestingly when these drugs were given concurrently, ODP was rescued. To further explore the effect of early alcohol exposure on ODP, we used Visually Evoked Potentials to examine the potentiation and depression components of ODP. Ethanol exposed and saline control animals were MD for 5, 7 or 10 days during the critical period of the visual cortex. Here we saw that although saline animals exhibited a normal depression of contralateral eye responses and a potentiation of ipsilateral eye responses, ethanol animals exhibited only a depression of contralateral eye responses. Additional ethanol animals were then MD for 3 days to test for changes in the on-set of contralateral eye depression. Yet, these animals exhibited normal contralateral eye response changes. In conclusion early ethanol exposure disrupts only the potentiation of the ipsilateral eye inputs, while leaving the contralateral eye response depression in tact. This model provides a new approach to studying ODP after early alcohol exposure, opening the door for studies using transgenic animals to further elucidate the mechanisms behind these alcohol induced deficits