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.

项目概要 动物如何协调它们的许多部分以产生连贯的、适应性的行为？有没有神经 协调整个动物神经活动从而协调整个动物行为的机制？ 对哺乳动物进行的大量低分辨率研究揭示了自发脑的高度保守的层次结构 跨越广泛频率范围的宽振荡，其中较慢、更全局的振荡似乎 通过各种跨频耦合机制协调和约束更快、更多的局部振荡。 然而，缓慢的全局振荡是否以及如何协调整个大脑的活动，从而协调整个动物的活动？ 由于测量、操作和建模整个哺乳动物的困难，行为仍然模糊不清 具有高时空分辨率的大脑。幸运的是，自发的全脑振荡也已被证实。 在斑马鱼、蜜蜂、果蝇，甚至刺胞动物、九头蛇中都发现了这种物质，这表明它们具有重要的进化意义 这些振荡的守恒，特别是超慢（0.01-0.1 Hz）节律。九头蛇拥有最简单的 已知的神经系统，并允许在行为过程中同时对其整个神经系统进行钙成像， 能够与单细胞分辨率同时观察所有节律。此外，Hydra 表现出强大的 使用机器学习对行为进行分类和量化，从而可以精确关联 具有细粒度行为的全局神经活动。因此，在这里我建议使用这个高度易于处理的系统来测试 假设 Hydra 的自发超慢网络——节律电位 1（RP1，0.1-0.01 Hz）—— 作为全局神经活动的组织者和协调者，以产生统一、连贯的行为。我预测 RP1 活动的破坏将导致全局神经活动混乱和行为不协调，如 初步数据表明。这里提出的研究将直接测试自发性之间的因果关系 超慢振荡和全局神经活动和行为。为了阐明 RP1 在 Hydra 中的作用，我首先 采用单神经元分辨率全神经系统钙成像和行为分析来确定是否 RP1 活动可预测全局神经活动和行为，以及它是否调节其他主要神经活动和行为。 通过跨频耦合在动物中建立网络。接下来，我将确定是否开发不同的RP1 网络与不同且不协调的全局神经活动和行为的发展相关 正在萌芽的九头蛇。然后我将从物理上、光学上和药理学上破坏 RP1 网络，以确定它是否 干扰会导致全局神经活动和行为不协调。总之，该提案将阐明 神经科学中一个尚未解答的主要问题：自发神经活动，特别是超慢神经活动的作用 振荡，以及它们是否可以协调全局神经活动和行为。该项目还将 为我提供开展成功的独立研究生涯所需的培训。