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 神经元是极化细胞的发现以及信号从树突传递到细胞体的推论 轴突使Ramon y Cajal能够确定神经元之间的连通性和神经元的流动方向 大脑中的信息。神经元连接中断是神经系统疾病的特征，年龄- 相关的智力下降，以及受伤后运动功能的丧失。这项建议解决了这个问题：是细胞 神经元功能所必需的极性？ 神经元的极性将在九头蛇身上解决，九头蛇是水母的淡水近亲。九头蛇有一个非常简单的， 分散的神经系统，称为神经网络，但表现出复杂的行为，包括点头，摇摆- 仰卧起坐、翻筋斗和对环境刺激的反应。九头蛇神经元缺乏明显的形态极性 而且没有显示轴突和树突的明显证据，这表明它们没有极化。另一方面 另一方面，有一些线索表明九头蛇可能有神经元的极性：它们有极化的化学突触和 轴突起始节段的遗传成分。此外，九头蛇还包含一套进化进化的核心-- 在高等生物体的神经元中供应与细胞极性有关的蛋白质。因此，无论是九头蛇- Ron的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极化，有许多细胞和分子标准 提出了区分轴突和树突的方法。这些标准将在目标1中进行测试，包括轴突长度， 直径，分支点的数量，微管的极性，肌动蛋白和中间丝的组织。 为了评估这些标准，该提案将利用新的分子工具 它允许对单个细胞进行荧光标记，并对其组成蛋白进行定位。在AIM 2，将检查通过九头蛇神经网络的信息流的性质。通过对神经元活动进行成像 感觉刺激后的钙感受器，即信号在神经中定向移动的程度 NET将会被确定。在目标3中，将使用数学模型来预测神经元结构是如何出现的。 从轴突的分枝和生长规律出发，通过研究再生模型对模型进行检验。 这些目标的完成将评估神经元极性在多大程度上是 神经功能，或者它是否是作为集中神经系统的特化而进化的。这些实验 将提供对高等动物和人类神经系统进化的洞察，是迈向 理解关系在行为中的作用的长期目标。不管极性和非极性 定向信号对神经元的功能和行为是必要的，拟议的研究有望 深入了解神经系统的功能和功能障碍。