Dynamic network reconfiguration at the transition between motor programs

运动程序之间转换时的动态网络重新配置

• 批准号: BB/T003146/1
• 负责人: Wenchang Li
• 金额: $ 56.15万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT003146%2F1
• 关键词: Dynamic; network; reconfiguration; transition; between

A beautiful ballerina dance can be considered as a continuous chain of motor actions (behaviours) such as jump, forward run, backward run, etc. Neurobiological experiments show that each particular motor behaviour can be characterised by a set of neurons producing a pattern of electrical activity. However, transitions between different patterns are poorly understood. Neurons are interconnected to form a neuronal network but it is not clear how the network can switch from one behaviour to another. What happens in the neuronal network when the forward run in a dance switches to backward? In this project, we will study young frog tadpoles with just two rhythmic motor behaviours: forward swimming and backward struggling. In swimming, alternation in neuron activity on each side leads to rapid waves of muscle contraction propagating from head to tail. If held by a predator, or stuck against an obstacle, the tadpole must quickly escape. In that case, it rapidly switches to the struggling behaviour, during which slower, but more stronger waves propagate from tail to head, leading to a powerful backward movement, which could be critical for survival. Of particular interest to us, is that the neuronal network that produce struggling is the same network that produces swimming. When the tadpole is captured by a predator, the continuous sensation on its skin results in the activation of extra groups of nerve cells while other groups of nerve cells are turned off. This means that the network reconfigures itself automatically to generate a different behaviour, potentially assisting the animal to escape. This fast reconfiguration to produce a different behaviour also occurs in more sophisticated brain networks in higher vertebrates and humans. Neuroscientists are devising new optical imaging methods to monitor the activity of groups of nerve cells in these complicated systems. In the tadpole, however, we can directly record from individual nerve cells in pairs, to measure precisely how their activity and the messages they exchange are altered at the transition between swimming and struggling. Thus, the tadpole provides an unparalleled ability to define and understand exactly what happens during neuronal network reconfiguration. Most fundamental neuronal mechanisms are highly conserved across vertebrate species. The results from tadpoles will be immensely useful to further understanding of more complex brain networks in mammals.The extremely detailed recordings that we can perform on the tadpole will also allow us to build detailed computer models of tadpole neuronal network involved in its motor control. These models will be used to examine the effects of manipulations of the network that are impossible to study experimentally and generate important insights. This way, the models can formulate new hypotheses that may be in turn tested experimentally. Using this combination of models and physiological recordings, we will understand 1) why the struggling waves are more powerful than the swimming waves; 2) why they propagate from tail to head, contrary to the head-to-tail propagation in swimming; and 3) how the neuronal circuit changes itself to produce these distinct behaviours. The findings will have implications beyond basic neuroscience research. For example, the principles could be used to better design robots that need to navigate difficult environments without getting stuck.

美丽的芭蕾舞可以被认为是一系列连续的运动动作(行为)，如跳跃、向前跑、向后跑等。神经生物学实验表明，每种特定的运动行为都可以由一组神经元产生一种电活动模式来表征。然而，人们对不同模式之间的转换知之甚少。神经元相互连接以形成神经元网络，但尚不清楚该网络如何从一种行为切换到另一种行为。当舞蹈中的向前跑切换到向后跑时，神经网络中会发生什么？在这个项目中，我们将研究只有两种有节奏的运动行为的幼蛙蝌蚪：向前游泳和向后挣扎。在游泳中，两侧神经元活动的交替导致肌肉收缩的快速波从头部传播到尾部。如果被捕食者抓住，或者卡在障碍物上，蝌蚪必须迅速逃脱。在这种情况下，它会迅速切换到挣扎的行为，在这个过程中，较慢但更强的波从尾巴传播到头部，导致强大的后退运动，这可能是生存的关键。我们特别感兴趣的是，产生挣扎的神经网络和产生游泳的神经网络是一样的。当蝌蚪被捕食者捕获时，它皮肤上的持续感觉导致额外的神经细胞群激活，而其他神经细胞群被关闭。这意味着这个网络会自动重新配置自己，以产生不同的行为，可能会帮助动物逃脱。这种产生不同行为的快速重组也发生在高等脊椎动物和人类更复杂的大脑网络中。神经学家正在设计新的光学成像方法，以监测这些复杂系统中神经细胞组的活动。然而，在蝌蚪身上，我们可以直接记录成对的单个神经细胞，以准确地测量它们的活动和它们交换的信息在游泳和挣扎之间的转变是如何改变的。因此，蝌蚪提供了一种无与伦比的能力，可以准确地定义和理解神经元网络重新配置期间发生的事情。大多数基本的神经机制在脊椎动物中是高度保守的。来自蝌蚪的结果将对进一步了解哺乳动物更复杂的大脑网络非常有用。我们可以在蝌蚪上进行极其详细的记录，这也将使我们能够建立与其运动控制有关的蝌蚪神经网络的详细计算机模型。这些模型将被用来检验网络操纵的影响，这些操纵不可能通过实验研究并产生重要的见解。通过这种方式，这些模型可以提出新的假设，而这些假设可能会在实验中得到检验。使用这种模型和生理记录的组合，我们将理解1)为什么挣扎的波比游泳波更强大；2)为什么它们从尾巴传播到头部，而不是游泳中从头到尾的传播；以及3)神经元电路如何改变自己来产生这些不同的行为。这些发现将产生超出基础神经科学研究的影响。例如，这些原理可以用来更好地设计需要在不陷入困境的环境中导航的机器人。

项目成果

Making In Situ Whole-Cell Patch-Clamp Recordings from Xenopus laevis Tadpole Neurons.

从非洲爪蟾蝌蚪神经元进行原位全细胞膜片钳记录。

• DOI: 10.1101/pdb.prot106856
• 发表时间: 2021
• 期刊: Cold Spring Harbor protocols
• 作者: Li WC

The early development and physiology of Xenopus laevis tadpole lateral line system.

• DOI: 10.1152/jn.00618.2020
• 发表时间: 2021-11-01
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Saccomanno V;Love H;Sylvester A;Li WC
• 通讯作者: Li WC

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression.

• DOI: 10.3390/ijms23052741
• 发表时间: 2022-03-01
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Kumar S;Kumar V;Li W;Kim J
• 通讯作者: Kim J

Mechanisms Underlying the Recruitment of Inhibitory Interneurons in Fictive Swimming in Developing Xenopus laevis Tadpoles.

• DOI: 10.1523/jneurosci.0520-22.2022
• 发表时间: 2023-02-22
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Ferrario, Andrea;Saccomanno, Valentina;Zhang, Hong-Yan;Borisyuk, Roman;Li, Wen-Chang
• 通讯作者: Li, Wen-Chang

Whole animal modelling reveals neuronal mechanisms of decision-making and reproduces unpredictable swimming in frog tadpoles

整体动物模型揭示了决策的神经元机制并重现了青蛙蝌蚪不可预测的游泳

• DOI: 10.1101/2021.07.13.452162
• 发表时间: 2021
• 作者: Ferrario A