Mechanisms of Neuron-Glia Synaptic Communication

神经元-胶质细胞突触通讯的机制

基本信息

批准号：
9769917
负责人：
Bruce H Appel
金额：
$ 19.44万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9769917
关键词：
Affect Animals Axon Brain CRISPR/Cas technology Cell Lineage Chemical Synapse Cognition Communication Coupled Data Electrophysiology (science)Electroporation Foundations Future Gene Expression Genes Genome Goals Growth Image Investigation Knowledge Learning Learning Skill Length Mediating Membrane Metabolic Methods Modification Molecular Motor Mus Myelin Myelin Sheath Neuraxis Neurobiology Neuroglia Neurons Oligodendroglia Pattern Performance Positioning Attribute Process Proteins Proteolipids Research Signal Transduction Synapses Synaptic Transmission Synaptic Vesicles Technical Expertise Testing Thick Time Tissues Transcript Transgenic Organisms Vertebrates Work Zebrafish behavior test cell type developmental neurobiology experience experimental study genetic manipulation imaging modality imaging study in utero in vivo insight loss of function myelination nervous system disorder neural circuit neurotransmission novel oligodendrocyte lineage oligodendrocyte precursor precursor cell protein function response skill acquisition transcriptome transcriptome sequencing zebrafish genome

项目摘要

Project Summary How axons are selectively ensheathed by specific amounts of myelin is a fundamental and unsolved problem in neurobiology. Myelin, produced by oligodendrocytes in the central nervous system of vertebrate animals, enhances axonal conduction of electrical impulses and provides axons with metabolic support. Evidence accumulated over the past several years indicates that myelination can adapt to neuronal activity, and that adaptive myelination is essential for learning and new skill development. The next important step is to identify the molecular functions that mediate communication between neurons and oligodendrocytes to facilitate adaptive myelination. Building on our own evidence that activity-evoked axonal vesicular secretion promotes myelin sheath growth, we hypothesize that proteins that function in synaptic communication between neurons also mediate synaptic-like signaling between axons and oligodendrocytes. We will test this hypothesis using zebrafish and mice, building on our expertise in zebrafish genome modification, mouse in utero electroporation and imaging of oligodendrocyte lineage cells in both species. Our experimental plan has two parts. First, we will investigate the expression and subcellular localization of synaptic proteins identified by RNA-seq profiling of oligodendrocyte lineage cell transcripts. Second, we will initiate loss-of-function studies to learn if synaptic proteins promote myelin sheath growth in vivo. This project has the potential to reveal important new mechanistic insights to adaptive myelination and the results will create a foundation for future, detailed investigations of axon- oligodendrocyte communication.

项目摘要轴突如何通过特定量的髓磷脂选择性地围墙是一个基本且未解决的问题神经生物学。髓磷脂，由脊椎动物中枢神经系统中的少突胶质细胞产生，增强电脉冲的轴突传导，并为轴突提供代谢支持。证据在过去的几年中积累的积累表明髓鞘化可以适应神经元活动，并且自适应髓鞘化对于学习和新技能发展至关重要。下一个重要步骤是确定介导神经元和少突胶质细胞之间通信以促进适应性的分子函数髓鞘。基于我们自己的证据，表明活动诱发的轴突囊肿分泌可以促进髓鞘鞘生长，我们假设在神经元之间突触通信中起作用的蛋白质也介导轴突和少突胶质细胞之间的突触样信号传导。我们将使用斑马鱼检验该假设和小鼠，基于我们在斑马鱼基因组修饰方面的专业知识，子宫电穿孔中的鼠标和两种物种中少突胶质细胞细胞的成像。我们的实验计划有两个部分。首先，我们会的研究通过RNA-seq分析鉴定的突触蛋白的表达和亚细胞定位少突胶质细胞谱系细胞转录本。其次，我们将启动功能丧失研究以了解突触蛋白质在体内促进髓鞘的生长。该项目有可能揭示重要的新机械对适应性髓鞘的见解，结果将为未来的轴突详细研究奠定基础。少突胶细胞通信。