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到细胞体传播的推论 轴突允许 Ramon y Cajal 确定神经元之间的连接以及神经元流动的方向 大脑中的信息。神经元连接的破坏是神经系统疾病、年龄相关疾病的特征 相关的精神衰退和受伤后运动功能丧失。该提案解决了以下问题：细胞是 极性对于神经元功能至关重要？ 神经元极性将在水螅（水母的淡水亲戚）中得到解决。九头蛇有一个非常简单的， 分散的神经系统，称为神经网络，却表现出复杂的行为，包括点头、摇摆 翻筋斗、翻筋斗以及对环境刺激的反应。水螅神经元缺乏明显的形态极性 并且没有显示出轴突和树突的明显证据，表明它们没有极化。另一方面 另一方面，有一些线索表明水螅可能具有神经元极性：它们具有极化的化学突触和 轴突起始段的遗传成分。此外，九头蛇包含一组核心的进化概念 提供与高等生物神经元细胞极性相关的蛋白质。因此，无论是Hydra neu- 电子极化是一个悬而未决的问题。 为了确定水螅中的神经元是否极化，需要采用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，包括神经突长度、 直径、分支点数量、微管极性以及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 水螅和它允许单个细胞被荧光标记，并且它们的组成蛋白被定位。瞄准 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 感觉刺激后的钙传感器，信号通过神经定向移动的程度 净值将被确定。在目标 3 中，数学模型将用于预测神经元结构如何出现 根据神经突分支和生长规则，模型将通过研究再生进行测试。 这些目标的完成将评估神经元极性在多大程度上是一个重要组成部分 神经元功能，或者它是否进化为中枢神经系统的专门化。这些实验 将提供对高等动物和人类神经系统进化的深入了解，并且是朝着 了解联系在行为中的作用的长期目标。无论极性与否 定向信号对于神经元功能和行为是必要的，拟议的研究预计将 提供对神经系统功能和功能障碍的深入了解。