In Vivo Time-Lapse Imaging of Retinal Synaptogenesis

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DESCRIPTION (provided by applicant): Highly specific and reproducible patterns of neuronal connectivity are established during development of the central nervous system (CNS). Individual neurons remodel their neuritic architecture based on relative levels of electrical activity. Most, if not all, neurological disorders result from disruption of these "synaptogenic" processes. Because neuronal synapse formation is a highly dynamic process, the ability to watch these events as they occur - preferably in the intact nervous system - will greatly enhance efforts to elucidate the mechanisms responsible for regulating both synaptogenesis and synaptic modulation. This proposal will utilize in vivo time-lapse imaging to investigate the cellular and molecular mechanisms that regulate synaptic contacts, organized into functionally distinct laminae, during development of the zebrafish retina. This system has many advantages: (i) synaptic laminae within the retina are well-characterized, (ii) the fish retina develops rapidly, (iii) the eye is transparent and therefore ideal for live imaging, (iv) transgenic and molecular manipulation techniques are established, (v) transgenic zebrafish lines exist in which subsets of retinal neurons express fluorescent marker proteins, and (vi) mutant fish in which retinal development and/or neuronal lamination is perturbed are available. The results of this study will provide the foundation for future studies aimed at addressing the mechanisms that organize synaptic development at the molecular, cellular and network levels.