Development of a model system for presynaptic study

项目描述（由申请人提供）：本项目旨在建立斑马鱼双极细胞作为研究带状视网膜神经元释放神经递质相关分子的系统。斑马鱼是一种优秀的脊椎动物生理和疾病模型，有利于大规模的诱变筛选和快速廉价的转基因动物的产生。因此，已经产生了一些作为人类疾病模型的突变体，未来还将开发出更多的突变体。我们打算将这种制备方法扩展到视觉建立后带状突触突触前末端的生理学研究。本提案旨在开发工具和技术来操纵和研究这些细胞的突触前过程。目的1建立两种斑马鱼制剂，用于研究视网膜神经元的神经递质释放和囊泡循环。Aim 2产生了几个转基因系，用于监测视网膜神经元的胞吐和内吞特性。目的3试图开发新的工具来沉默成年斑马鱼的基因表达。神经系统中的信息在突触的神经细胞之间传递，在突触前神经细胞中的电脉冲导致神经递质从被称为突触囊泡的小膜结合结构中释放出来。这一过程的缺陷被认为是许多神经系统疾病的病理基础和促成因素，包括亨廷顿氏病、阿尔茨海默病、双相情感障碍、精神分裂症、帕金森病和智力低下，但尚不清楚这些疾病如何影响突触前功能。本研究为研究突触前神经细胞如何释放神经递质提供了新的工具。

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.