Variation in postpartum maternal care programs the development of neuroendocrine and mesolimbic dopamine pathways in female offspring

Variation in adult rat maternal behavior is predicted by the experience of maternal licking and grooming (LG) in infancy, such that females that experience high levels of LG (High LG) during postnatal development typically themselves become High LG dams, and females that experience low levels of LG become Low LG dams. Experience of high maternal LG also predicts elevated estrogen receptor-alpha (ERalpha) and oxytocin receptor levels in brain regions critical for maternal behavior such as the medial preoptic area of the hypothalamus. The first series of experiments within this thesis demonstrates that these neuroendocrine differences in ERalpha-immunoreactivity and mRNA emerge in offspring during the postnatal period (postnatal days 0-21). These studies also show postnatal emergence of epigenetic alterations of the ERalpha gene (Esr1), including DNA methylation and chromatin remodeling, in response to maternal care. Furthermore, this research reveals sensitive periods during postnatal development for maternal LG to affect gene expression and onset of maternal behavior in juvenile offspring. The mesolimbic dopamine system is also critically implicated in adult maternal behaviors, and was hypothesized to be responsive to variation in maternal LG. A second series of studies demonstrate that low or high levels of maternal LG predict levels of dopamine neurons in the ventral tegmental area, an effect that emerges during the postnatal period and lasts through adulthood. These neurobiological changes within the ventral tegmental area may be shaped by maternal LG-associated effects on postnatal levels of transcription factors that contribute to development of the mesolimbic dopamine system. Reward-directed behaviors known to be dependent upon mesolimbic dopamine function were also found to be different among offspring of High or Low LG dams. Finally, a third series of experiments reveal that over-expressing ERalpha in the medial preoptic area beginning early in postnatal development is sufficient to enhance maternal behaviors, and increase the level of dopaminergic cells in the ventral tegmental area in offspring reared by Low LG dams to the level of those reared by High LG dams. This finding suggests that ERalpha is a mediating factor for the effect of maternal LG on offspring maternal behavior. Together, these studies show that the quality of the maternal environment early in life programs long-lasting alterations in two brain systems critical for complex behaviors such as maternal and reward-directed behaviors.