Regulation Of Neuronal Gene Expression By Action Potenti

Child Health And Human Development

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Abstract

Research in the Unit on Neurocytology and Physiology, is concerned with understanding how the brain develops and modifies its structure and function through experience. Functional activity in the brain during late stages of fetal development and in early postnatal life is essential for normal development of the nervous system of higher vertebrates. Our research is investigating the molecular mechanisms that enable neural impulse activity to regulate major developmental processes of both neurons and glia. This main objectives of this research program are: (1) to understand how the expression of genes controlling the developing structure and function of the nervous system are regulated by patterned neural impulse activity; (2) to determine the functional consequences of neural impulse activity on major developmental processes, including: cell proliferation, survival, differentiation, growth cone motility, axon bundling (fasciculation), neurite outgrowth, synaptogenesis and synapse remodeling, myelination, interactions with glia, and the mechanisms of learning and memory in postnatal animals; (3) to understand how information contained in the temporal pattern of neural impulse activity is transduced and integrated within the intracellular signaling networks of neurons to activate specific genes and control appropriate adaptive responses. Major achievements of research in the last year include: (1) the discovery that development of glia of the peripheral and central nervous system (Schwann cells and oligodendrocytes) is regulated by neural impulse activity in premyelinated neurons, and determined that extracellular ATP and related molecules communicate neural impulse activity in neurons to glia; (2) tested the hypothesis that a key signaling protein activated by neural impulse activity and involved in LTP, calcium-calmodulin dependent protein kinase II (CaM KII) can decode different frequencies of action potentials by autophosphorylation at Thr-286; (3) determined that different calcium-dependent signaling pathways are activated in CA1 neurons by different stimulus patterns to phosphorylate the signaling molecule MAPK in association with long-term potentiation (LTP) in the hippocampus; used DNA microarrays to study gene expression profiles in neurons in response to specific patterns of neural impulses.