The long term goal of this project is to determine the cues that guide axonal growth, synaptogenesis and synaptic modification in the developing vertebrate brain. Here, we propose to examine in vivo the growth, differentiation and modification of optic nerve axons in the frog Xenopus laevis. The growth and branching of individual optic nerve fibers will be followed as they grow into and branch to form terminal arbors within their primary target, the optic tectum, using low light level video microscopy, laser scanning confocal microscopy and two-photon laser scanning microscopy. The ability to observe identified axons in vivo offers the rare opportunity to experimentally dissect the signals that guide axonal growth in a biologically relevant setting. The experiments will exploit our recent progress in showing that the neurotrophin BDNF is a relevant factor for visual system development in frog. The experiments will extend the previous results, which showed that the changing the levels of BDNF in the target tissue rapidly and dramatically altered the branching pattern of the optic nerve fibers. In particular, the experiments will: -explore the consequences of BDNF-mediated signaling in the retinotectal projection; - determine the interactions between neuronal activity and the action(s) of neurotrophins; - employ fusion proteins to follow the assembly of synaptic specializations. The experiments will extend approaches typically used only in culture by using modern imaging technologies to permit the living, intact nervous system to be studied. As such, they offer a rare glimpse into the dynamics of synaptic patterning and the integration between multiple cues in forming patterned neural networks.
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