CRCNS Research Project: Solving the neural code of Hydra

破译复杂的生物学问题的一种方法，如了解大脑是如何工作的，是通过使用更简单的系统来实现更多的实验或计算访问。九头蛇是水母的一种小而透明的近亲，代表着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，覆盖着动物的身体，没有神经节或大脑。尽管这种简单性，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造的九头蛇品系，在这种品系中，神经元和肌肉的活动会导致它们产生光信号。因此，研究人员可以直接观察到动物在行为时每个神经元和肌肉细胞的激活情况。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。他们发现了简单神经系统如何控制肌肉产生行为的基本原理。鉴于九头蛇没有大脑，这个项目可能会揭示复杂的运动是如何在没有任何中央协调的情况下组织起来的。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动物的很小的部分重塑。了解九头蛇的神经网如何在快速更替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。采用综合成像/计算方法的九头蛇研究是一个吸引外展机会的平台。这项研究向普通公众介绍了神经成像、基本生物学和数学神经科学。它还为各级研究人员提供了培训机会。九头蛇系统被深度整合到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、其控制的肌肉和肌肉使用九头蛇产生的行为之间的关系。研究人员专注于破译一些基本行为的神经基础，这些基本行为可以被严格识别，并由内胚层和外胚层神经网络产生。研究人员在收缩行为中使用了安装在九头蛇制剂中的每个神经元和每个肌肉细胞的钙成像。为了分析所需的数据集，研究人员开发了算法来跟踪移动、变形的动物中的细胞，并应用降维方法来发现与肌肉激活模式相对应的运动的时空模式。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，为跟踪神经元和发现时空模式而开发的技术在开放源码平台上得到了广泛使用，并可能在其他系统中使用。这项拟议的工作将有助于将九头蛇建立为一个模型神经系统，可以严格地对神经活动和行为进行完整的核算。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.