Development of a model system for presynaptic study

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DESCRIPTION (provided by applicant): The goal of this project is to establish the zebrafish bipolar cells as a system for studying the molecules involved neurotransmitter release from ribbon-type retinal neurons. Zebrafish are an excellent vertebrate model for physiology and disease, conducive to both large-scale mutagenesis screens and the rapid and cheap generation of transgenic animals. Hence, several mutants have been generated that serve as human disease models and many more will be developed in the future. We intend to extend the utility of this preparation to the study of the physiology of presynaptic terminals from ribbon-type synapses after vision has been established. This proposal aims at developing tools and techniques for manipulation and investigation of presynaptic processes in these cells. Aim 1 establishes two zebrafish preparations for studying neurotransmitter release and vesicle recycling from retinal neurons. Aim 2 generates several transgenic lines for monitoring the properties of exocytosis and endocytosis in retinal neurons. Aim 3 attempts to develop new tools for silencing gene expression in adult zebrafish. Information in the nervous system is transmitted between nerve cells at the synapse, where an electrical impulse in the "presynaptic" nerve cell causes the release of neurotransmitter from small membrane bound structures, known as synaptic vesicles. Deficiencies in this process have been suggested to underlie and contribute to the pathologies of a number of neurological disorders, including Huntington's disease, Alzheimer's disease, bipolar disorder, Schizophrenia, Parkinson's Disease and mental retardation, yet it is unclear how presynaptic function is affected by these disorders. This proposal develops new tools to study how presynaptic nerve cells release neurotransmitter.