Early-Life Stress: Rodent Models, Lessons and Challenges

The maturation of the nervous system involves multiple dynamic processes that are regulated both by genetic factors and environmental input. Although some of these processes are complete at birth, the early postnatal brain is far from mature and continues to undergo significant developmental processes; these processes include axonal and dendritic growth, synaptic stabilization, and synaptic pruning. The perinatal period therefore represents a critical stage of development, rendering the brain particularly vulnerable to organizing (and disorganizing) environmental influences. Indeed, when stress is experienced during this critical early-life period, its impacts on brain function can be long-lasting or even permanent, compared to the typically transient effects of stress on the adult brain. Years of research in the neuroscience and neuroendocrine fields have therefore focused on identifying the mechanisms by which early-life stress (ELS) regulates brain development. In mammals, including humans and rodents, maternal input has perhaps the most influence on what type of environment developing offspring experience. Not surprisingly, most animal models of ELS target that interaction, disturbing either the quantity and/or quality of maternal care during early life. Such models have become widely adopted, and from this vast literature it is clear that the ultimate outcome of ELS depends on the 'stressful' nature of the experience: its quality, severity, and duration. Models that consist of chronic or severe stress manipulations, the focus of the current chapter, have found that such forms of developmental stress have long-lasting consequences for the structure and function of several brain networks, ultimately modulating the output of multiple emotional and cognitive behaviors. The implementation and interpretation of these models, including their advantages, disadvantages, and application to the human condition, will be discussed throughout this chapter.