Neural mechanisms of behavioral coordination in Hydra

项目摘要 动物如何协调它们的许多部分来产生连贯的、适应性的行为？是否有神经 协调整个动物神经活动从而协调整个动物行为的机制？ 许多对哺乳动物的低分辨率研究揭示了一个高度保守的自发性脑的层次结构， 广泛的振荡跨越广泛的频率范围，其中更慢，更全球性的振荡似乎， 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，是否以及如何缓慢的全球振荡可能协调整个大脑活动，从而，整个动物， 由于难以测量、操纵和模拟整个哺乳动物， 具有高时空分辨率的大脑幸运的是，自发的全脑振荡也被 在斑马鱼，蜜蜂，果蝇，甚至刺胞动物Hydra vulgaris中发现，表明重要的进化 这些振荡的保守性，特别是超低（0.01-0.1 Hz）的节奏。九头蛇拥有最简单的 已知的神经系统，并允许其整个神经系统在行为期间的同时钙成像， 使得能够与单细胞分辨率并行地观察所有节律。此外，Hydra表现出强大的 已经使用机器学习进行分类和量化的行为， 精细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Hydra-rhythm potential 1（RP 1，0.1- 0.01Hz）的自发超低频网络- 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 RP 1活动的中断将导致无序的全局神经活动和不协调的行为， 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关系。 超低频振荡和全局神经活动和行为。为了阐明RP 1在Hydra中的作用，我将首先 采用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 RP 1活性可以预测整体神经活动和行为，以及它是否调节其他主要的神经活动。 通过交叉频率耦合在动物的网络中。接下来，我将确定不同RP 1的发展是否 神经网络与不同的和不协调的全球神经活动和行为的发展相关， 初出茅庐的九头蛇然后，我将在物理上、光学上和物理上中断RP 1网络，以确定其 中断导致不协调的全局神经活动和行为。总之，这一建议将阐明 神经科学中一个尚未回答的主要问题：自发神经活动的作用，特别是超慢 振荡，以及它们是否可以用于协调全球神经活动和行为。该项目还将 为我提供所需的培训，以开展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.