The C. elegans locomotion nervous system: an integrated multi-disciplinary approach

线虫运动神经系统：综合的多学科方法

• 批准号: EP/C011961/1
• 负责人: Netta Cohen
• 金额: $ 61.65万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FC011961%2F1
• 关键词: C.; elegans; locomotion; nervous; system

C. elegans is one of the simplest creatures of the animal kingdom. With a mapped genome and the only mapped neural circuitry, this organism offers a first tangible opportunity to understand an entire living, behaving and learning system bottom-up and top-down. As such, it offers great promise to systems biologists, neuroscientists and roboticists alike. Despite its relative simplicity, C. elegans possesses many of the functions that are attributed to higher level organisms, including feeding, mating, complex sensory abilities, memory and learning. Can we understand the underlying engineering designs that allow this tiny nematode to survive and flourish? What insight can we gain into universal principles that give rise to adaptive and robust life-forms or to the unique architecture of its nervous system? Meeting this challenge requires a large multi-disciplinary effort, combining insight and expertise from biology, physics, engineering and computer science.The proposed research focuses on achieving a step change in our understanding of the C. elegans locomotion system and its neural control. At the modelling level, current theoretical models of the locomotion subsystem of C. elegans rely on genomic data, the known neural circuitry, limited behavioural and electrophysiological experiments on C. elegans and knowledge from other related species. All in all the knowledge base for this modelling feat is very incomplete and hence all models to date make a large number of unconfirmed assumptions. Very fundamental questions, such as whether the locomotion system relies on endogenous control in the form of central pattern generation, have recently been debated. These questions can be addressed in mathematical and simulation models; however, the physical environment (pressure, friction, sensory inputs) may be too complex to incorporate reliably in a model. I propose to construct robotic models of the nematode, incorporating alternative predicted models of neuronal circuits and to test them under a variety of physical conditions, mimicking behavioural experiments on the biological worm. This project involves three levels of investigation: First, systematic behavioural studies of the locomotion of the worm; second, the construction, analysis and simulation of detailed neurocomputational models of the locomotion system; and third, the construction of robotic models and their testing.At the technological level, probing the activity of C. elegans neurons and muscles has eluded electrophysiogists due to the mechanical properties of the worm. Hence, despite some progress, it is remarkably difficult to confirm or further develop models of neuronal subsystems such as the locomotion subsystem. At the same time, C. elegans is transparent and hence amenable to fluorescence recordings. Efforts are underway to develop voltage-sensitive dyes for sensory neurons, but to date, C. elegans neurons or muscle cells have not been fluorescently recorded from. I propose to develop molecular voltage probes to directly record the voltage-activity of C. elegans locomotion muscles. This effort builds on my preliminary work in which quantum dots (semiconductor nanoparticles) have been embedded in biological membranes. The next steps involve obtaining a voltage-response from these probes and embedding them in cells of living animals. The ability to monitor the voltage activity in behaving animals should lead to a step change in our understanding of the locomotion system in particular and the C. elegans motor system in general. Furthermore, implementation of this technology should constitute a major advance that extends much beyond the study of C. elegans to a wide range of scientific and industrial applications in both biological and bioinspired engineering domains.

C.秀丽线虫是动物王国中最简单的生物之一。有了绘制的基因组和唯一绘制的神经回路，这种生物体提供了第一个切实的机会来了解整个生活，行为和学习系统自下而上和自上而下。因此，它为系统生物学家、神经科学家和机器人学家提供了巨大的希望。尽管它相对简单，C。线虫具有许多属于高级生物的功能，包括进食、交配、复杂的感觉能力、记忆和学习。我们能理解让这种微小的线虫生存和繁荣的潜在工程设计吗？我们能对产生适应性强的生命形式或其神经系统独特结构的普遍原理有什么见解？应对这一挑战需要大量的多学科努力，结合生物学，物理学，工程学和计算机科学的洞察力和专业知识。线虫运动系统及其神经控制在模型化水平上，目前的C。秀丽隐杆线虫依赖于基因组数据、已知的神经回路、有限的行为和电生理学实验。以及其他相关物种的知识。总而言之，这一建模壮举的知识基础非常不完整，因此迄今为止的所有模型都做出了大量未经证实的假设。非常基本的问题，如运动系统是否依赖于中央模式生成形式的内源性控制，最近一直在争论。这些问题可以在数学和仿真模型中解决;然而，物理环境（压力，摩擦，感官输入）可能过于复杂，无法可靠地纳入模型中。我建议构建机器人模型的线虫，纳入替代预测模型的神经元电路，并在各种物理条件下测试它们，模仿行为实验的生物蠕虫。该项目包括三个层次的研究：第一，系统的蠕虫运动行为研究;第二，运动系统的详细神经计算模型的构建、分析和模拟;第三，机器人模型的构建和测试。由于线虫的机械特性，电生理学家一直无法研究线虫的神经元和肌肉。因此，尽管取得了一些进展，但很难确认或进一步开发神经元子系统（如运动子系统）的模型。同时，C.秀丽隐杆线虫是透明的，因此适合于荧光记录。人们正在努力开发用于感觉神经元的电压敏感染料，但到目前为止，C。elegans神经元或肌肉细胞尚未被荧光记录。我建议开发分子电压探针，直接记录C的电压活性。运动肌肉这项工作建立在我的初步工作基础上，其中量子点（半导体纳米颗粒）已嵌入生物膜中。接下来的步骤包括从这些探针中获得电压响应，并将它们嵌入活体动物的细胞中。监测行为动物的电压活动的能力应该会导致我们对运动系统的理解发生一步变化，特别是C。elegans运动系统一般。此外，这项技术的实现应该构成一个重大的进步，远远超出了C语言的研究。elegans在生物和生物启发工程领域的广泛科学和工业应用。

项目成果

Gait Modulation in C. Elegans: It's Not a Choice, It's a Reflex!

• DOI: 10.3389/fnbeh.2011.00010
• 发表时间: 2011
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Boyle JH;Berri S;Tassieri M;Hope IA;Cohen N
• 通讯作者: Cohen N

Gait Modulation in C. elegans: An Integrated Neuromechanical Model.

• DOI: 10.3389/fncom.2012.00010
• 发表时间: 2012
• 期刊: Frontiers in computational neuroscience
• 影响因子: 3.2
• 作者: Boyle JH;Berri S;Cohen N
• 通讯作者: Cohen N

Power and Wavelength Dependence of Photoenhancement in (CdSe)ZnS-Dopamine in Aqueous Solution and Live Cells

• DOI: 10.1524/zpch.2008.6012
• 发表时间: 2008-05
• 期刊: Zeitschrift für Physikalische Chemie
• 作者: S. Clarke;S. Koshy;J. Zhang;Netta Cohen;J. Nadeau