Mechanisms of Nitric Oxide and Neurotrophin Regulation of Nerve Growth Cone Motility

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

0080932 LeTourneau Function of the nervous system depends on correct wiring of synaptic connections that communicate information between neurons or between neurons and other targets, such as muscles. Axons make these connections during fetal development by extending through intervening tissues to reach the targets where they make regularly patterned connections. Growing axons are guided by extrinsic positive and negative guidance cues. Two of these cues, nitric oxide and the neurotrophin BDNF are involved in regulating the formation of axonal branches in target organs. The proposed experiments will examine how growing retinal axons integrate signals from these tips, growth cones, to establish proper connections between the eye and the brain. Tissue culture studies show that axonal tips, growth cones, collapse when exposed to nitric oxide, but if the growth cones are first exposed to BDNF and then nitric oxide, they are stabilized against nitric oxide-induced collapse. The project goals are to clarify the intracellular molecular singaling that mediates regulation of axon terminal development. Nitric oxide and BDNF are implicated in a wide range of activities that involve structural changes in neural connections. The mechanisms that underlie the structural plasticity of early development are relevant to ongoing functions on the mature nervous system, such as learning, memory and repair of injuries. Better understanding of these mechanisms will help develop strategies to improve nervous function and better treat injuries and diseases of the brain.