The capacity for the mature brain to undergo functional reorganization is well appreciated.However, many questions remain as to the degree of this plasticity beyond early stages of development.There remains a vast gulf between understanding how molecules, cells and neural circuits respond in adaptive ways to regimes that modify function and the effectiveness of therapies that are used to restore function after brain injury or disease.Thus, major challenges of modern neuroscience at the interface of biology and medicine are to: (1) identify plasticity mecha nisms that are resilient to developmental down-regulation, (2) understand how to re-activate plasticity processes that are developmentally regulated and (3) to bridge the gap between the principles of plasticity established in the laboratory and interventions and therapies offered in the clinic.