Examining cell polarity in nerve nets

检查神经网络中的细胞极性

• 批准号: 10259695
• 负责人: Ashley L Arthur
• 金额: $ 4.19万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-03-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259695
• 关键词: Action Potentials; Address; Age-associated memory impairment; Animal Behavior; Animal Model; Animals; Architecture; Axon; Behavior; Biological; Biological Process; Biophysics; Brain; Calcium; Caliber; Cell Polarity; Cells; Characteristics; Chemical Synapse; Chemicals; Cnidaria; Cognitive; Complex; Cues; Cytoskeleton; Decentralization; Deductibles; Dendrites; Electron Microscopy; Evolution; Exhibits; Fingerprint; Foundations; Fresh Water; Functional disorder; Glean; Goals; Growth; Hallmark Cell; Human; Image; Individual; Injury; Intermediate Filaments; Interneurons; Jellyfish; Label; Learning; Length; Mediating; Methodology; Microfilaments; Microfluidics; Microtubules; Modeling; Molecular; Monitor; Morphology; Motor; Natural regeneration; Nature; Nerve Net; Nervous System Physiology; Nervous system structure; Neuraxis; Neurites; Neurodegenerative Disorders; Neurons; Organism; Outcome; Positioning Attribute; Process; Proteins; Psyche structure; Regenerative research; Role; Signal Transduction; Specificity; Stimulus; Stochastic Processes; Synapses; System; Testing; Transgenic Animals; Travel; age related; behavioral response; chemical genetics; experimental study; feeding; insight; knock-down; mathematical model; model development; molecular marker; nervous system disorder; neuron development; neuronal circuitry; neurotransmission; polarized cell; quantitative imaging; regeneration model; repaired; response; restoration; sensor; sensory stimulus; tool

Project Abstract The discovery that neurons are polarized cells and the deduction that signals travel from dendrites to cell bodies to axons allowed Ramon y Cajal to determine the connectivity between neurons and the direction of flow of information in the brain. Disruptions in neuronal connectivity are characteristic of neurological disease, age- related mental decline, and loss of motor function after injury. This proposal addresses the question: is cell polarity essential for neuronal function? Neuronal polarity will be addressed in Hydra, freshwater relatives of jellyfish. Hydra have a very simple, decentralized nervous system, called a nerve net, yet demonstrate complex behaviors including nodding, sway- ing, somersaulting, and responding to environmental stimuli. Hydra neurons lack obvious morphological polarity and do not show clear evidence of axons and dendrites, suggesting that they are not polarized. On the other hand, there are some clues that Hydra may have neuronal polarity: they have polarized chemical synapses and genetic components of the axon initial segment. Furthermore, Hydra contain a core set of evolutionarily con- served proteins that are associated with cell polarity in neurons of higher organisms. Thus, whether Hydra neu- rons are polarized is an open question. To determine whether or not neurons in Hydra are polarized, a number of cellular and molecular criteria that distinguish axons and dendrites are proposed. These criteria, to be tested in Aim 1, include neurite length, diameter, number of branch points, microtubule polarity, and the organization of actin and intermediate filaments. To assess these criteria, the proposal will take advantage of new molecular tools that are becoming available in Hydra and which allow individual cells to be fluorescently labeled, and their constituent proteins localized. In Aim 2, the nature of information flow through Hydra nerve nets will be examined. By imaging neuronal activity with calcium sensors following a sensory stimulus, the extent to which signals move directionally through the nerve net will be determined. In Aim 3, mathematical models will be used to predict how neuronal architecture emerges from neurite branching and growth rules, and the models will tested by studying regeneration. Completion of these aims will assess the extent to which neuronal polarity is an essential component of neuronal function, or whether it evolved as a specialization of centralized nervous systems. These experiments will provide insight into the evolution of nervous systems in higher animals and humans and is a step toward a long-term goal of understanding the role of connections in behavior. Regardless of whether or not polarity and directional signaling are necessary for neuronal function and behavior, the proposed studies are expected to provide insight into the function and dysfunction of the nervous system.

项目摘要 发现神经元是偏振细胞的发现，以及信号从树突传播到细胞体 到轴突使拉蒙·凯加尔（Ramon Y Cajal）确定神经元之间的连通性和流动方向 大脑中的信息。神经元连通性的破坏是神经疾病的特征，年龄 - 相关的精神下降和受伤后运动功能的丧失。该建议解决了一个问题：是单元格 神经元功能必不可少的极性？ 神经元的极性将在水母的淡水亲戚Hydra中解决。九头蛇很简单， 分散的神经系统称为神经网，但表现出复杂的行为，包括点头，摇摆 对环境刺激进行响应，并响应环境刺激。九头蛇神经元缺乏明显的形态极性 并且不要显示轴突和树突的明确证据，表明它们不是极化的。另一方面 手，有一些线索表明Hydra可能具有神经元极性：它们具有偏振化学突触和 轴突初始段的遗传成分。此外，Hydra包含一组进化的核心 较高生物体神经元中与细胞极性相关的蛋白质。因此，是否hydra neu- 罗恩斯两极分化是一个悬而未决的问题。 为了确定九头蛇中的神经元是否两极分化，许多细胞和分子标准 提出了区分轴突和树突。这些标准将在AIM 1中进行测试，包括神经突长度， 直径，分支点数，微管极性以及肌动蛋白和中间细丝的组织。 为了评估这些标准，该提案将利用新的分子工具的优势 Hydra并允许单个细胞被荧光标记，并将其组成蛋白定位。目标 2，将检查信息流通过九头蛇网的性质。通过对神经元活性进行成像 钙传感器遵循感觉刺激，信号在神经方向上移动的程度 净将确定。在AIM 3中，数学模型将用于预测神经元结构的出现 来自神经突的分支和生长规则，模型将通过研究再生来测试。 这些目的的完成将评估神经元极性是多大程度的程度 神经元功能，还是它作为集中神经系统的专业发展。这些实验 将提供有关上等动物和人类神经系统演变的见解，这是迈向 理解联系在行为中的作用的长期目标。不管是极性和是否 方向信号传导对于神经元功能和行为是必要的，预计拟议的研究将是 提供有关神经系统功能和功能障碍的洞察力。