Development of a model system for presynaptic study

突触前研究模型系统的开发

基本信息

批准号：
7924298
负责人：
DAVID Paul ZENISEK
金额：
$ 8.43万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-01 至 2010-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924298
关键词：
Adult Affect Alzheimer&apos s Disease Animals Binding Biological Models Bipolar Disorder Caliber Cell Line Cells Clathrin-Coated Vesicles Color Communities DNA Development Disease Disease model Electric Capacitance Electrical Synapse Electrophysiology (science)Endocytosis Exhibits Exocytosis Fishes Fluorescence Microscopy Foundations Future Gene Expression Gene Silencing Generations Genes Genetic Goals Heat-Shock Proteins 70 Heat-Shock Response Heating Histocompatibility Testing Huntington Disease Image Individual Investigation Kinetics Location Mammalian Cell Measurement Measures Membrane Mental Retardation MicroRNAs Modeling Molecular Monitor Movement Mus Mutagenesis Nervous system structure Neurons Noise Organism Parkinson Disease Pathology Phenotype Physiological Physiology Plants Polymerase Preparation Presynaptic Terminals Process Property Proteins Rattus Recycling Repression Retinal Ribosomes Schizophrenia Scientist Signal Transduction Slice Structure Synapses Synaptic Vesicles System Techniques Tissues Transcript Transgenic Animals Transgenic Mice Transgenic Organisms Vesicle Vision Xenopus Zebrafish cell type human disease knock-down mature animal mutant nervous system disorder neurotransmitter release overexpression presynaptic pri-miRNA promoter research study retinal bipolar neuron retinal neuron small hairpin RNA tool trafficking voltage clamp

项目摘要

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.

描述（由申请人提供）：该项目的目标是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的分子的系统。斑马鱼是一种优秀的生理学和疾病脊椎动物模型，有利于大规模诱变筛选和快速、廉价地产生转基因动物。因此，已经产生了几种突变体作为人类疾病模型，并且未来还将开发更多突变体。我们打算将这种制剂的用途扩展到视觉建立后带状突触突触前末梢的生理学研究。该提案旨在开发用于操纵和研究这些细胞中突触前过程的工具和技术。目标 1 建立了两种斑马鱼制剂，用于研究视网膜神经元的神经递质释放和囊泡回收。目标 2 产生多个转基因系，用于监测视网膜神经元胞吐作用和内吞作用的特性。目标 3 尝试开发新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输，“突触前”神经细胞中的电脉冲导致神经递质从小膜结合结构（称为突触小泡）释放。这一过程中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、帕金森病和智力迟钝，但尚不清楚突触前功能如何受到这些疾病的影响。失调。该提案开发了新工具来研究突触前神经细胞如何释放神经递质。