Neural mechanisms of behavioral coordination in Hydra

水螅行为协调的神经机制

• 批准号: 10505359
• 负责人: Alison Hanson
• 金额: $ 17.09万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10505359
• 关键词: Adaptive Behaviors; Address; Adult; Affect; Animal Behavior; Animals; Bees; Behavior; Behavioral; Behavioral Mechanisms; Brain; Calcium; Cells; Cnidaria; Complex; Computer Models; Coupling; Data; Development; Drosophila genus; Etiology; Exhibits; Frequencies; Fruit; Grain; Hallucinogens; Human; Image; Light; Link; Lysergic Acid Diethylamide; Machine Learning; Mammals; Measures; Modeling; Molecular; Nervous system structure; Neurons; Neurosciences; Operative Surgical Procedures; Opsin; Optics; Organism; Parents; Pattern; Periodicity; Pharmaceutical Preparations; Pharmacology; Play; Reporting; Research; Resolution; Role; System; Testing; Training; Transgenic Organisms; Zebrafish; behavioral study; career; experimental study; foot; neural network; neuromechanism; neuropsychiatric disorder; neuropsychiatry; optogenetics; promoter; relating to nervous system; spatiotemporal

PROJECT SUMMARY How do animals coordinate their many parts to generate coherent, adaptive behavior? Are there neural mechanisms that coordinate whole animal neural activity thereby coordinating whole animal behavior? Numerous low-resolution studies in mammals have revealed a highly conserved hierarchy of spontaneous brain- wide oscillations spanning a wide range of frequencies in which slower, more global oscillations appear to coordinate and constrain faster, more local oscillations via various cross-frequency coupling mechanisms. However, whether and how slow global oscillations might coordinate whole brain activity and, thus, whole animal behavior, remains obscure due to the difficulty of measuring, manipulating, and modeling whole mammalian brains with high spatiotemporal resolution. Fortunately, spontaneous brain-wide oscillations have also been found in zebrafish, bees, fruit flies, and even the cnidarian, Hydra vulgaris, indicating significant evolutionary conservation of these oscillations, particularly the ultraslow (0.01-0.1 Hz) rhythms. Hydra possesses the simplest known nervous system and allows simultaneous calcium imaging of its entire nervous system during behavior, enabling observation of all rhythms in parallel with single cell resolution. In addition, Hydra exhibits robust behaviors that have been categorized and quantified using machine learning, allowing precise correlation of global neural activity with fine-grained behavior. Thus, here I propose to use this highly tractable system to test the hypothesis that the spontaneous ultraslow network of Hydra—rhythmic potential 1 (RP1, 0.1-0.01 Hz)— serves as an organizer and coordinator of global neural activity to generate unified, coherent behavior. I predict that disruption of RP1 activity will result in disorganized global neural activity and uncoordinated behavior, as preliminary data indicate. The studies proposed here will directly test the causal link between spontaneous ultraslow oscillations and global neural activity and behavior. To elucidate the role of RP1 in Hydra, I will first employ single neuron resolution whole nervous system calcium imaging and behavioral analysis to determine if RP1 activity is predictive of both global neural activity and behavior and whether it regulates the other major networks in the animal via cross-frequency coupling. Next, I will determine if development of distinct RP1 networks is correlated with development of distinct and uncoordinated global neural activity and behavior in budding Hydra. I will then disrupt the RP1 network physically, optically, and pharmacologically to determine if its disruption results in uncoordinated global neural activity and behavior. Together, this proposal will shed light on a major unanswered question within neuroscience: the role of spontaneous neural activity, particularly ultraslow oscillations, and whether they might serve to coordinate global neural activity and behavior. This project will also provide me with the training I need to launch a successful independent research career.

项目摘要 动物如何协调许多部分以产生连贯的自适应行为？有中立 协调整个动物神经活动的机制，从而协调整个动物行为？ 在哺乳动物中进行的许多低分辨率研究表明，赞助商的高度层次结构 广泛的振荡跨越了广泛的频率，在这些频率中，似乎更慢，全球振荡似乎 通过各种跨频耦合机制来更快地协调和约束，更局部振荡。 但是，全球振荡是否以及如何速度可以协调整个大脑活动，因此，整个动物 行为，由于难以测量，操纵和建模整个哺乳动物，因此仍然晦涩难懂 具有高时空分辨率的大脑。幸运的是，赞助商范围的振荡也已经 在斑马鱼，蜜蜂，水果蝇，甚至是cnidarian的Hydra ufgaris中发现，表明明显的进化 这些振荡的保存，特别是Ultraslow（0.01-0.1 Hz）节奏。九头蛇拥有最简单的 已知的神经系统，并允许行为过程中同时对其整个神经系统进行钙成像， 与单细胞分辨率并联观察所有节奏。此外，Hydra表现出强大的 使用机器学习对已经进行了分类和量化的行为，从而可以精确地相关 具有细粒度行为的全球神经活动。那我在这里建议使用这个高度易处理的系统进行测试 Hydra的赞助超速网络 - 节律电位1（RP1，0.1-0.01 Hz） - 是全球中性活动的组织者和协调员，以产生统一的连贯行为。我预测 RP1活性的破坏将导致杂乱无章的全球神经活动和不协调的行为，因为 初步数据指示。这里提出的研究将直接测试赞助之间的因果关系 Ultraslow振荡以及全球神经活动和行为。为了阐明RP1在Hydra中的作用，我将首先 员工单神经元分辨率全神经系统钙成像和行为分析，以确定是否是否 RP1活性可以预测全球神经活动和行为，以及它是否调节另一个主要 动物中的网络通过跨频耦合。接下来，我将确定是否开发不同的RP1 网络与在不同的全球神经活动和行为的发展相关 萌芽的九头蛇。然后，我将在物理，光学和药物上破坏RP1网络，以确定其是否是否 破坏导致不协调的全球神经活动和行为。该提议在一起将阐明 神经科学中的一个主要未解决的问题：赞助神经元活动的作用，尤其是Ultraslow 振荡以及它们是否可以协调全球神经活动和行为。这个项目也将 为我提供成功的独立研究职业所需的培训。