of the nooptokinetic response cmutant showing that this behavior doesnot require retinal ON pathways. During positive phototaxis, correctlyaligned larvae suppress further orienting movements and activatemotor patterns for swimming. We asked whether the dopaminergicsystem modulates swimming during phototaxis. In pharmacologicalexperiments, we found that the dopamine agonist apomorphine altersorientation behavior, converting negative phototaxis into positivephototaxis. At higher doses, apomorphine increased both the frequencyand extent of swim bouts with distinct effects mediated by D1 and D2receptors. Consistent with a role for the dopaminergic system inmodulating swimming behaviors, too few mutant larvae, which havereductions in discrete populations of monoaminergic neurons, showimpaired phototaxis compared to wildtype sibling fish. Goal directedbehavior in zebrafish larvae can thus be understood as the product ofsequentiallyactivated locomotormaneuvers,whose initiation frequencyis modulated by forebrain monoaminergic systems.

doi:10.1016/j.ntt.2012.05.031

NBTS 31Behavioral phenotyping of two mouse lines with reducedantioxidant capacity

Chris Currana, Ying Chenb, Daniel Nebertb, Krishna Patelb, MichaelWilliamsc, Charles VorheescaNorthern Kentucky University, Highland Heights, KY, United StatesbUniversity of Cincinnati College of Medicine, Cincinnati, OH,United StatescCincinnati Children's Research Foundation, Cincinnati, OH, United States

High glucose metabolism in the brain requires effective antiox-idant protection, and many neurological disorders are associated withhigh levels of oxidative stress. To better understand the impact ofreduced antioxidant capacity on the developing brain, we conductedbehavioral phenotyping of two mouse lines with reduced antioxidantcapacity: the Gulo(−/−) mouse, which is incapable of producingascorbage, and the Glcm(−/−) mouse, which has chronically lowlevels of glutathione. Although the Gulo(−/−) mice were supple-mented with a minimum level of ascorbate in drinking water toprevent scurvy, the mice did show lower activity and slower swimspeeds in Morris water maze testing. Interestingly, the mice alsoexhibited an exaggerated response to the methamphetamine in theopen field, suggesting that ascorbate deficiency causes striataldysfunction. In contrast, Gclm(−/−) mice not only showed sub-normal anxiety in the elevated zero maze, and slightly faster swimspeeds in Morris water maze, but also had an exaggerated response tomethamphetamine. These results suggest that the developing brainhas at least some level of resiliency to reduced antioxidant capacity.

doi:10.1016/j.ntt.2012.05.032

NBTS 32A framework to study gene–environment interactions inchild development

Robert WrightHarvard School of Public Health, Cambridge, MA, United States

A collaborative approach to studying gene–environment interactioncould have immediate impact on our understanding of how environ-mental factors induce developmental disease and toxicity and willprovide biological insight for potential treatment and preventionmeasures. Because DNA sequence is static, genetic studies typically are

not conducted prospectively. This limits the ability to incorporateenvironmental data into an analysis, as such data are usually collectedcross-sectionally in genetic studies. Prospective environmental datacollection could account for the role of critical windows of susceptibilitythat likely correspond to the expression of specific genes and genepathways. The use of large-scale genomic platforms to discovergenetic variants that modify environmental exposure in conjunctionwith a-priori planned replication studies would increase the speed ofdiscovery and validate findings by reducing the number of false positiveresults. However, the measurement of environmental risk factorslongitudinally is expensive and most environmental health studieshave populations <1000 participants. Genomewide studies likely needsample sizes much larger than this. Pooling resources across multiplecohorts may be a cost effective method to conduct GXE interactionresearch that incorporates genomics, environmental exposures, andcritical developmentalwindows. A logical starting point for such studieswould be pediatric birth cohorts. Using a genome-wide approach,combined with prospective longitudinal measures of environmentalexposures at critical developmental windows, is the optimal design forgene–environment interaction research. Perinatal/childhood diseasesare ideal for organizing consortiums dedicated to studying GXEinteraction. This approach would discover susceptibility variants, andthen validate the findings in independent samples of children. Designsthat combine the strengths andmethodologies of environmental healthand genetics will yield data that can account for both genetic variabilityand the role of critical developmental windows in the etiology ofchildhood disease and development. Finally, a consortium of birthcohorts would yield additional value such as the potential to studychemical mixtures, as well as epigenetic changes, both of which wouldbe benefit from prospective exposure data.

doi:10.1016/j.ntt.2012.05.033

NBTS 33The consequences of barriers to prenatal care in less developedcountries: Important lessons for everyone

Janet HardyXcenda, Tampa, FL, United States

This presentation will identify factors and barriers to prenatal careand safe delivery in middle-income and low-resource countries. Caremay be impacted by, for example, the availability of skilled health careproviders; health care practice and system factors; service provision inrural, urban, or urban slumsettings; cultural beliefs andpractices; accessto affordable, effective and often life-savingmedications; nutrition; andother factors. The impact and scale such factors may have on pregnancycomplications, preterm delivery, spontaneous abortion or fetal death,major malformations, and maternal mortality can be far greater in lessdeveloped settings than in developed ones. These factors will bediscussed, compared, and contrasted. An example to highlight thisdiscussion will include the contributing factors and challenges in highrates of caesarean section and preterm delivery. A further example willaddress preeclampsia/eclampsia diagnosis, treatment, and the frequentconsequence of mortality. The second half of the presentationwill focuson innovation in prenatal/maternal care delivery in middle-income andlow-resource countries. Innovation from the perspective of technology(new versus new applications of existing technology), and from theperspective of innovative and effective methods of care delivery will bediscussed. Specific examples will illustrate high-impact yet low-costinnovation. This presentation will conclude with lessons learned.Typically, researchers, health care providers, and administrators attemptto translate knowledge and maternal health strategies from developedcountries to middle-income and low-resource countries. Some lessons

NBTS 2012 Abstracts378