Significance to Biomedical Research and the Program of the Institute

Nervous system development during prenatal and postnatal life is influenced in essential ways by functional activity, which regulates neuron and glial survival and the wiring of appropriate connections between neurons. The molecular mechanisms involved in these processes are not well understood. The signaling reactions and transcriptional regulatory mechanisms that control expression of genes in response to specific patterns of neural impulse activity must be understood to allow interventions in the developmental and regenerative remodeling of the nervous system, and to begin to address certain learning and memory dysfunctions on a molecular level. Cell adhesion molecules help determine the developing structure of the nervous system by controlling the physical interactions between neurons and glia during development and regeneration. Abnormalities in these molecules are associated with a wide range of developmental neurological disorders, including hydrocephalus, fetal alcohol syndrome, schizophrenia, learning and memory dysfunction. The signals and processes that control interactions between myelinating Schwann cells and axons are of great clinical interest. Abnormalities in myelination cause a wide range of neurological disorders due to defective impulse conduction, such as those associated with phenylketonuria, Tay-Sachs, Gaucher's disease, traumatic injury and compression ischemia, toxic agents, infections and metabolic disorders. ATP is released from damaged cells and may be involved in pathophysiological responses to hypoxia and nervous system trauma.