It may seem surprising that rather subtle variations in maternal behavior have such profound impact on development. However, for a rat pup, the first six weeks of life do not hold a great deal of stimulus diversity. Stability is the theme of the burrow, and the social environment in the first days of life is defined by the mother and the littermates. The mother then serves as the primary link between the environment and the developing animal. Following on these results, an important line of research, linked to pathway studies in humans that are the core of this report, is identification of the features of rat life histories and their relationship to gene expression that contribute to downstream health outcomes.

Another line of recent animal research having profound implications for future investigations in humans centers around evidence that individual differences in maternal behavior are transmitted across generations (in both rats and nonhuman primates). For example, in rats the female offspring of high LG-ABN mothers show significantly more licking and grooming and arched-back nursing than female offspring of low LG-ABN mothers (Francis et al., 1999). In rhesus monkeys there is clear evidence for inter-generational transfer of rejection of infants by mothers. The rate of rejection of infants by mothers correlated with the rejection rates of their mothers (Suomi, 1987; Suomi and Levine, 1998). In vervet monkeys, daughters reared by mothers who consistently spent a large amount of time in physical contact with their offspring became mothers who were similarly more attentive to their offspring (Fairbanks, 1989).

An important complement to these findings is evidence indicating that specific environmental events can alter trajectories of development not only in the affected offspring but also into the next generation (Francis et al., 1999). For example, biological offspring of low LG-ABN mothers cross-fostered onto high-LG-ABN mothers are indistinguishable from the natural progeny of high-LG-ABN mothers in terms of behavioral measures of fearfulness or of HPA axis response to stressful experiences. In addition, these behavioral effects are reflected in corresponding changes in CRF gene expression in the hypothalamus and amygdala. Moreover, in adult females of both the cross-fostered and natural progeny groups, their maternal behavior was typical of high-LG-ABN mothers. Similarly, the behavior of adult offspring of high-LG-ABN mothers reared by low-LG-ABN dams resembled that of the normal offspring of low-LG-ABN mothers.

An example relating directly to predisease pathways concerns cross-fostering between borderline hypertensive rats (BHR) and wild-type WKY mothers (Gouldsborough and Ashto, 1998; Sanders and Gray, 1997; Myers et al., 1989). The starting point for this investigation is the introduc-