Regulation Of Neuronal Gene Expression By Action Potenti

Child Health And Human Development

Investigators

Linked publications & trials

Abstract

Research in the Unit on Neurocytology and Physiology, is concerned with understanding the molecular mechanisms by which functional activity in the brain regulates development of the nervous system during late stages of fetal development and early postnatal live. The 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. 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 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 how gene expression is activated to convert a model of short-term memory into long-term memory (e-LTP to l-LTP)), and used DNA microarrays to obtain gene expression profiles in neurons in response to specific patterns of neural impulses.