Accumulating evidence indicates that several of the long-term consequences of prenatal alcohol exposure (PAE) are the result of changes in the development and function of cortico-limbic structures that regulate the hypothalamic-pituitary-adrenal (HPA) axis. We hypothesize that alterations in glucocorticoid programming in the hippocampal formation underlie many of the effects of PAE on neurogenesis, synaptic plasticity and learning and memory, and that the maternal and early-life environments can modify the aberrant glucocorticoid programming. We will use an approach that overlays our drinking-in-the-dark PAE mouse model with a housing system that influences pregnant dam and offspring stress, maternal - neonate interactions and the early-life social environment using a subtle, ethologically relevant method termed the communal nest. Our preliminary studies show that communal rearing improves learning and memory in a context discrimination test, as well as reduces anxiety-like and depressive-like behaviors, in the offspring. PAE animals display deficits in a variety of hippocampal-dependent learning and memory tests, hippocampal long term potentiation (LTP) and neurogenesis. Our hypothesis, supported by published findings and preliminary data, suggest that PAE produces a feed-forward stress drive within the central control of the HPA axis. Our studies will evaluate the mitigating effects of the maternal and early-life social environment on these PAE-induced phenotypes. In addition, we will evaluate if PAE-induced changes within the extended HPA axis can be moderated by the early social environment and if the PAE-induced changes in the stress axis play a key role in these observed deficits. These studies may provide a mechanistic basis for early maternal-infant intervention as a means of mitigating the deleterious effects of PAE.
This study will explore whether the effects of prenatal alcohol exposure can be moderated by the early social environment. Specifically, a mouse model of fetal alcohol exposure will be used to explore if communal rearing improves learning and memory and modulates stress reactivity in offspring, mitigating the effects of prenatal ethanol exposure