CRCNS Research Project: Solving the neural code of Hydra

破译复杂生物学问题的一种方法，例如理解大脑如何工作，是使用一个更简单的系统，使更多的实验或计算访问。水螅是水母的一种小而透明的亲戚，代表了第一批进化出神经系统的动物。相应地，九头蛇的神经系统非常简单，只有几百个神经元组成一个网状结构，没有神经节或大脑。尽管如此简单，九头蛇的神经网络产生了丰富的灵活行为，包括收缩，伸长，弯曲，搜索和翻筋斗。最近，该项目的研究人员开发了基因改变的水螅菌株，其中神经元和肌肉的活动使它们产生光信号。因此，研究人员可以直接观察动物行为时每个神经元和肌肉细胞的激活。正因为如此，他们可以使用统计方法来分析神经活动如何驱动运动。 他们发现了简单的神经系统如何控制肌肉产生行为的基本原理。考虑到九头蛇没有大脑，这个项目可能会揭示在没有任何中央协调的情况下，复杂的运动是如何组织起来的。此外，九头蛇有一种非凡的再生能力：它的细胞不断被替换，一个完整的九头蛇身体可以从即使是非常小的动物碎片改革。了解九头蛇的神经网络如何在快速周转的情况下继续产生稳定的行为，可能会促进对神经系统如何自我修复的理解。Hydra的研究与综合成像/计算方法作为一个有吸引力的平台外展机会。 这项研究向公众介绍了神经成像和基本生物学和数学神经科学。 它还为各级研究人员提供培训机会。Hydra系统被深度融入海洋生物实验室的暑期课程中，并为来自不同背景的学生提供交叉项目。该项目旨在破译神经系统活动之间的关系，它控制的肌肉和肌肉使用刺胞动物Hydra产生的行为。研究人员专注于解码一些基本行为的神经基础，这些行为可以被严格识别，并由内胚层和外胚层神经网络产生。研究人员使用钙成像的每一个神经元和每一个肌肉细胞在安装水螅准备在收缩行为。为了分析所需的数据集，研究人员开发了跟踪移动变形动物中细胞的算法，并应用降维方法来发现与肌肉激活模式相对应的运动时空模式。最终产品是一个定量模型，解释了收缩行为是如何产生的。作为另一个可交付成果，开发用于跟踪神经元和发现时空模式的技术在开源平台中广泛使用，并可能在其他系统中使用。这项拟议的工作将有助于建立九头蛇作为一个模型神经系统，其中一个完整的会计神经活动和行为可能会严格approached.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

One way to decipher a complex biological problem, such as understanding how the brain works, is by using a simpler system that enables greater experimental or computational access. Hydra is a small, transparent relative of the jellyfish, and represents the first animals to have evolved a nervous system. Correspondingly, the nervous system of Hydra is very simple, with a few hundred neurons forming a net which tiles the body of the animal, without ganglia or brain. In spite of this simplicity, Hydra's nerve net generates a rich range of nimble behaviors, including contracting, elongating, bending, searching and somersaulting. Recently, the investigators of this project developed genetically altered Hydra strains in which the activity of neurons and muscles causes them to generate a light signal. Thus, the investigators can directly observe the activation of every neuron and muscle cells in an animal while it is behaving. Because of this, they can use statistical methods to analyze how neural activity drives movements. They discover basic principles of how simple nervous systems control muscles to produce behaviors. Given that Hydra has no brain, this project may reveal how complex movement can be organized without any central coordination. Further, Hydra has an extraordinary ability to regrow: its cells are constantly being replaced, and a complete Hydra body can reform from even very small pieces of the animal. Understanding how the nerve net of Hydra continues to produce stable behavior in the face of rapid turnover may advance understanding of how nervous systems can repair themselves. The study of Hydra with an integrated imaging/computational approach serves as an appealing platform for outreach opportunities. The research introduces members of the general public to neuroimaging and essential biology and mathematical neuroscience. It also provides training opportunities for researchers at all levels. The Hydra system is deeply integrated into summer courses at the Marine Biological Laboratory and provides cross-cutting projects for students from diverse backgrounds.This project aims to decipher the relation between the activity of a nervous system, the muscles it controls and the behavior the muscles generate using the cnidarian Hydra. The investigators focus on decoding the neural basis of a few elementary behaviors that can be rigorously identified and that are generated by the endodermal and ectodermal nerve nets. The investigators use calcium imaging of every neuron and every muscle cell in mounted Hydra preparations during contractile behaviors. To analyze the required data sets, the investigators develop algorithms to track cells in the moving, deforming animal and apply dimensionality reduction methods to discover spatiotemporal patterns of movement corresponding to muscle activation patterns. The end product is a quantitative model that explains how contractile behaviors are generated. As another deliverable, the techniques developed to track neurons and discover spatiotemporal patterns are made widely available in an open source platform and may be of use in other systems. This proposed work will help establish Hydra as a model neural system for which a complete accounting of neural activity and behavior may be rigorously approached.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.