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

Abstract

Background Neuronal plasticity deficits are thought to underlie abnormal neurodevelopment in Fetal Alcohol Spectrum Disorders (FASD) and in animal models of this condition. Previously, we found that alcohol exposure during a period that is similar to the last months of gestation in humans disrupts ocular dominance plasticity (ODP), as measured in superficial cortical layers. We hypothesize that exposure to alcohol can differentially affect the potentiation and depression of responses that are necessary for activity dependent sprouting and pruning of neuronal networks. ODP is an established paradigm that allows the assessment of activity-dependent depression and potentiation of responses in vivo. Methods Mouse pups were exposed to 3.6 – 5g/kg of ethanol in saline daily or every other day between postnatal days 4 and 9. Visual cortex plasticity was then assessed during the critical period for ODP using two techniques that separately record in layers 4 (visual evoked potentials, VEPs) and 2/3 (optical imaging of intrinsic signals, OI). Results We discovered a layer-specific effect of early alcohol exposure. Recording of VEPs, from layer 4, showed that while the potentiation component of ODP (Pc-ODP) was disrupted in animals treated with alcohol when compared to saline controls, the depression component of ODP (Dc-ODP) was unaltered. In contrast, OI, from layers 2/3, showed that Dc-ODP was markedly disrupted in alcohol treated animals when compared to controls. Conclusions Combined with our previous work, these findings strongly suggest that developmental alcohol exposure has a distinct and layer-specific effect on the potentiation and depression of cortical responses after monocular deprivation.

Developmental alcohol exposure impairs synaptic plasticity without overtly altering microglial function in mouse visual cortex

“…2). Agreeing with prior literature, we found that without deprivation, EtOH mice had a contralateral eye bias no different from that of either SEP or SAL controls (Lantz et al, 2015). After 4 days of contralateral eye monocular deprivation, BGS EtOH treated mice exhibited ODIs that were not significantly different from those in the ND EtOH group, demonstrating that the ocular dominance shift toward the open eye did not occur properly.…”

“…We focused on assessing microglial phenotype in the visual cortex, a brain region showing deficits in experience-dependent synaptic plasticity in early adolescent mice following our model of BGS EtOH exposure (Fig. 2, (Lantz et al, 2015)). Because recent studies have implicated microglia as critical players in experience-dependent plasticity, we hypothesized that BGS EtOH might alter the physiological phenotype of microglia in a way that would impair synaptic plasticity.…”

“…For example, exposing rats to EtOH throughout gestation leads to negative outcomes for adult somatosensory cortex neuronal function: spontaneous activity is dramatically decreased and the ability of these neurons to undergo plasticity in response to whisker trimming is severely impaired (Rema and Ebner, 1999). Deficits in experience-dependent plasticity within the visual cortex, specifically ocular dominance plasticity (ODP), have also been demonstrated after BGS EtOH exposure (Lantz et al, 2015; Lantz et al, 2012; Medina et al, 2003; Medina and Ramoa, 2005). A detailed understanding of this specific plasticity deficit is relevant to the human condition, as FASD patients often have difficulties with visual perception because of poor visual acuity and sensitivity to contrast (Doney et al, 2016; Vernescu et al, 2012).…”

“…In both adolescent ferrets and mice, the ocular dominance bias of animals that remain non-deprived after EtOH exposure during the BGS is no different from that of controls. However, when animals previously exposed to EtOH undergo monocular deprivation for either short (3–4 days) or longer periods (10 days) during the visual critical period, they exhibit defects in their ability to shift ocular dominance toward the open eye (Lantz et al, 2015; Lantz et al, 2012; Medina et al, 2003). It has been shown in ferrets that the BGS EtOH-induced impairment of ODP is present regardless of when monocular deprivation is initiated during the visual critical period (Medina and Ramoa, 2005).…”

“…In this study, we used a mouse model of developmental EtOH exposure that resulted in reductions in ODP in early adolescence (Lantz et al, 2015; Lantz et al, 2012). To understand whether microglia contribute to this ODP defect, we conducted an extensive analysis of microglial phenotypes in early adolescent animals after developmental EtOH exposure.…”