Research in the Section on Nervous System Development and Plasticity, 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 life. The two 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 the last year include showing that myelination is regulated by electrical activity, and that the mechanism involves astrocytes releasing LIF in response to ATP liberated by axons firing action potentials. LIF stimulates myelination by mature oligodendrocytes. Other achievements include identifying changes in gene expression associated with conversion of e-LTP to l-LTP, a cellular model for conversion of short-term to long term memory; identifying activity-dependent interactions between neurons and glia, including how myelination in the PNS and CNS is regulated by axonal firing; detecting an adenosine receptor in Schwann cells (A2a receptor) that is important in regulating Schwann cell development according to action potential firing; identifying intracellular calcium signaling networks regulating gene expression and synaptic plasticity; and identifying genes that are abnormally expressed in a peripheral nerve sheath tumor.
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