All modern conceptualizations of the relative roles of genetic and environmental influences on behavioral development emphasize the interactive nature of these factors. However, few studies of mammalian behavioral ontogeny have explicitly assessed the nature of these interactions by simultaneously comparing prenatal (uterine) and postnatal (maternal) environmental effects on animals of different genetic backgrounds. To demonstrate such interactions, in the proposed project mice from two strains (C57BL/6J and BALB/cJ) with distinct behavioral profiles will be transferred, as embryos, to recipient females of either their own or the other strain. Pups born from these mothers will then be cross-fostered to mothers of either their own or the other strain. The design will thus be a full parametric of genetic line, uterine environment, and postnatal maternal environment, allowing partitioning of these components. More important, the results will be analyzed for two- and three-way interactions of these components. A large number of dependent behavioral outcomes will be measured, beginning during the postnatal period with naturalistic assessment of mother-infant interaction, growth, maternal responsiveness, and pup vocalization responses to separation. After weaning, subjects' emotionality will be assessed by open field reactivity, behavior in an elevated plus-maze, Porsolt's swim test, and a novel object test. Finally, spatial learning will be assessed in a Morris water maze test. In additional to analyzing each of these measures separately for main and interactive effects, the relationship between individual differences in early postnatal factors (e.g., maternal responsiveness) and subsequent behavioral outcomes will be examined. ? ? The results will provide a demonstration project for how gene-environment interactions can be assessed that will be applicable to analysis of these factors in any of the large number of inbred, selectively-bred and genetically-manipulated strains of mice that are now available. In addition to addressing basic questions of gene-environment interaction, application of these procedures could elucidate some of the mechanisms by which genetic variants express different developmental trajectories. Basic information about the roles played by pre- and early postnatal environment may ultimately be important, as well, for our understanding of some of the potential behavioral consequences of various assisted reproductive technologies, such as gestational surrogacy, that are becoming more common in clinical practice. ? ?
