Early alcohol exposure disrupts visual cortex plasticity in mice

Abstract

There is growing evidence that deficits in neuronal plasticity underlie the cognitive problems seen in fetal alcohol spectrum disorders (FASD). However, the mechanisms behind these deficits are not clear. Here we test the effects of early alcohol exposure on ocular dominance plasticity (ODP) in mice and the reversibility of these effects by phosphodiesterase (PDE) inhibitors. Mouse pups were exposed to 5 g/kg of 25% ethanol i.p. on postnatal days (P) 5, 7 and 9. This type of alcohol exposure mimics binge drinking during the third trimester equivalent of human gestation. To assess ocular dominance plasticity animals were monocularly deprived at P21 for 10 days, and tested using optical imaging of intrinsic signals. During the period of monocular deprivation animals were treated with vinpocetine (20mg/kg; PDE1 inhibitor), rolipram (1.25 mg/Kg; PDE4 inhibitor), vardenafil (3 mg/Kg; PDE5 inhibitor) or vehicle solution. Monocular deprivation resulted in the expected shift in ocular dominance of the binocular zone in saline controls but not in the ethanol group. While vinpocetine successfully restored ODP in the ethanol group, rolipram and vardenafil did not. However, when rolipram and vardenafil were given simultaneously ODP was restored. PDE4 and PDE5 are specific to cAMP and cGMP respectively, while PDE1 acts on both of these nucleotides. Our findings suggest that the combined activation of the cAMP and cGMP cascades may be a good approach to improve neuronal plasticity in FASD models.

Effects of Developmental Alcohol Exposure on Potentiation and Depression of Visual Cortex Responses

“…Surprisingly, the effect of early alcohol exposure on ODP as assessed by VEPs seems to be much less robust than what our laboratory has previously observed using optical imaging of intrinsic signals (Lantz et al, 2012). In our previous study, 10 days of MD did not result in any distinguishable change in CBIs in alcohol exposed mice, suggesting that both Pc- ODP and Dc-ODP were disrupted.…”

“…This finding was intriguing because in our previous study using optical imaging of intrinsic signals (OI), alcohol treated animals did not show an OD shift after 10 days of MD (Lantz, et a; 2012). While these prior findings strongly suggested an effect of alcohol on both Pc-ODP and Dc-ODP, it is difficult to tease apart the contributions of these individual components using OI.…”

“…or saline as a control on days P5, 7 and 9. According to our previously published studies, this protocol leads to blood alcohol levels of 411 mg/dl (± 43) at 1 hour post injection (Lantz et al, 2012). …”

“…The recorded field potential represents the summation of the responses from many neurons, but is primarily composed of responses from layer 4, as indicated by the depth of the electrode implantation (~430nm), as well as the VEP size and polarity (largest negative polarity VEP is a result of direct thalamic input into layer 4 of the primary visual cortex; Heynen and Bear, 2001). Optical imaging of intrinsic signals has historically also been used to investigate ODP in rodents (Kalatsky and Stryker, 2003; Lantz et al, 2012; (Lehmann and Lowel 2008). The origin of these intrinsic signals lies in the changes in oxy-hemoglobin and hemoglobin with tissue activation, these signals are now considered to arise predominately from superficial cortical layers such as layer 2/3 (Frostig and Chen-Bee, 2009; Lee et al, 2012; McCurry et al, 2010; Smith et al, 2009; Bonhoeffer 1995).…”

“…We showed that alcohol exposure from postnatal day 10 (P10) to P30 in ferrets or between P5-P9 in mice, periods that are roughly equivalent to the last months of human gestation, leads to a permanent impairment in ODP (Medina et al, 2003; Lantz et al, 2012). However it is still unknown whether the neuronal plasticity impairments seen after alcohol exposure are due to a specific disruption of Pc-ODP, Dc-ODP, or both.…”