Thematic Initiatives 2007-2009


 The NIH Neuroscience Blueprint emerged from the premise that there are fundamental themes in neuroscience research that cross Institute and Center boundaries.  In fiscal years 2007, 2008, and 2009, Blueprint RFAs will focus on three themes, respectively: (1) neurodegeneration during disease and aging; (2) neurodevelopment throughout the lifespan; and (3) neuroplasticity, from the molecular level to the behavioral level.

Neurodegeneration - Scientists have known for many years that Alzheimer's and other neurological diseases in the elderly stem from neurodegeneration, a progressive dying-off of nerve cells. It's now known that neurodegeneration also occurs in many childhood neurological disorders, in adult-onset disorders such as epilepsy and multiple sclerosis, as a cause of visual and hearing loss, in the wake of stroke and trauma, during chronic pain syndromes, as a result of drug and alcohol abuse, and even in psychiatric disorders such as schizophrenia. It is likely that in at least some of these diverse conditions, nerve cells die because they are besieged by common insults, including damage by highly reactive "free radicals," over-excitation leading to "excitotoxicity," formation of abnormal aggregates of protein in cells, and activation of "cell suicide" programs. Strategies that target these mechanisms thus are likely to have widespread application for treating a variety of neurological diseases and injuries.

Neurodevelopment - How the nervous system develops is one of the great mysteries of biology, a puzzle whose solution has profound implications for the treatment of brain disorders and their behavioral consequences. Knowledge of nervous system development is progressing rapidly on many fronts, including the factors that control specialization of cells, which signals guide the formation of appropriate connections among nerve cells, and the mechanisms by which experience and genes work together to sculpt the nervous system. Understanding normal development provides insight into inherited disorders of the nervous system, developmental disorders such as cerebral palsy and autism, and the vulnerability of the developing brain to many types of insults. There is a tantalizing prospect that knowledge of development can be harnessed to slow or repair damage to the nervous system. Potential treatments emerging from studies of development include, for example, preventing nerve cell death with neurotrophic factors, reactivating or transplanting stem cells, and rewiring damaged nervous tissue through pharmacological means. An improved understanding of neurodevelopment – and a perspective that views aging and disease within that context – is necessary to translate these therapies from theory into practice.

Neuroplasticity - For most of the 20th century, the adult human brain was viewed as hard-wired – incapable of regenerating nerve cells and relatively poor at rearranging the connections between them. In the last two decades, however, mounting evidence has shown that the adult nervous system has remarkable plasticity, that is, the capacity to adapt to experience. Indeed, it is capable of forming new connections in response to injury, and even harbors stem cells capable of replacing lost nerve cells. The ability to harness this plasticity holds the promise of novel therapeutic approaches for disorders as diverse as stroke, addiction, and post-traumatic stress. Equally important evidence suggests that a dark side to brain plasticity may contribute to conditions such as dystonia, epilepsy, chronic pain states, drug and alcohol dependence, and depression. Understanding neural plasticity at all levels – from molecules and cells to physiology and behavior – thus has broad implications for treating neurological disease.