Mechanisms of Neuron-Glia Synaptic Communication

项目摘要 轴突是如何被特定数量的髓鞘选择性包裹的，这是一个基本的和尚未解决的问题。 神经生物学。髓鞘是由脊椎动物中枢神经系统中的少突胶质细胞产生的， 增强电脉冲的轴突传导，为轴突提供代谢支持。证据 过去几年的积累表明，髓鞘形成可以适应神经元的活动，并且 适应性髓鞘形成对学习和新技能的发展至关重要。下一个重要的步骤是确定 调节神经元和少突胶质细胞之间的通讯以促进适应的分子功能 髓鞘形成。基于我们自己的证据，即活动诱发的轴突囊泡分泌促进髓鞘 鞘的生长，我们假设在神经元之间的突触交流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。我们将用斑马鱼来验证这一假设 和小鼠，基于我们在斑马鱼基因组修改方面的专业知识，小鼠在子宫内的电穿孔和 这两个物种的少突胶质细胞系细胞的成像。我们的实验计划包括两个部分。首先，我们将 用RNA-seq图谱研究突触蛋白的表达和亚细胞定位 少突胶质细胞系细胞转录本。其次，我们将启动功能丧失研究，以了解突触是否 蛋白质在体内促进髓鞘生长。这个项目有可能揭示重要的新机制 对适应性髓鞘形成的见解和结果将为未来对轴突的详细研究奠定基础。 少突胶质细胞通讯。

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.