Neural Mechanisms of Behavioral Coordination in Hydra

项目总结 动物如何协调它们的多个部位，以产生连贯的、适应性的行为？他们有神经吗？ 协调整个动物神经活动从而协调整个动物行为的机制？ 大量对哺乳动物的低分辨率研究揭示了自发脑的高度保守的层次结构- 跨宽频率范围的宽振荡，其中较慢的、更全局的振荡似乎 通过各种交叉频率耦合机制协调和约束更快、更多的局部振荡。 然而，全球振荡是否以及缓慢程度可能会协调整个大脑活动，从而协调整个动物 行为，由于测量、操作和对整个哺乳动物建模的困难，仍然不清楚。 具有高时空分辨率的大脑。幸运的是，自发的全脑振荡也是 在斑马鱼、蜜蜂、果蝇，甚至刺蛇中发现，这表明了重大的进化 这些振荡的守恒，特别是超低(0.01-0.1赫兹)的节律。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质成像， 能够在单细胞分辨率的同时观察所有节律。此外，九头蛇还表现出了强大的生命力 已使用机器学习进行分类和量化的行为，允许精确关联 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处理的系统来测试 假设水力节律电位1(RP1，0.1-0.01赫兹)的自发超低网络- 作为全球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活动的中断将导致全球神经活动的混乱和行为的不协调，因为 初步数据显示。这里提出的研究将直接测试自发性之间的因果联系 超低振荡和全球神经活动和行为。为了阐明RP1在九头蛇中的作用，我首先 使用单个神经元分辨率、全神经系统钙成像和行为分析来确定 RP1活性可以预测全局神经活动和行为，以及它是否调节其他主要 通过交叉频率耦合在动物体内形成网络。接下来，我将确定不同的RP1的开发 网络与不同和不协调的全局神经活动和行为的发展相关 萌芽中的九头蛇。然后我将在物理上、光学上和药物上破坏RP1网络，以确定其 干扰会导致全球神经活动和行为的不协调。综上所述，这项提案将阐明 神经科学中的一个重大悬而未决的问题：自发神经活动的作用，特别是超低水平 振荡，以及它们是否可能起到协调全球神经活动和行为的作用。该项目还将 为我提供所需的培训，让我开始成功的独立研究事业。

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.