Molecular psychiatry has revealed a number of genes whose variants influence the risk to develop psychiatric disorders. However, the genetic predisposition alone does not predict if a disease will become manifest or not. Environmental factors, such as trauma, stress or infection also influence the development of psychiatric disorders. So both, genes and environment determine the individual risk. Animal models are useful tools to study the influences of genes and environmental factors on behavior and cognition, and to elucidate the underlying morphological and molecular changes. In this talk it will be presented that aversive experiences early in life and psychosocial stress during adolescence alter anxiety-like behavior in mice. In addition it will be shown that environmental enrichment and physical activity during different phases of life influence learning and memory, and the development of an Alzheimer-like pathology in APP transgenic mice. The associated neuropathological and compensatory substrates will be discussed.