Neural Control of Swimming in Zebrafish

*神经系统确保我们行动正常。为了做到这一点，神经系统必须设定我们移动的速度，协调我们所有的肌肉，使它们以有组织的方式行动，并确保我们身体的左右两侧协同工作。这些任务是由神经元完成的，最明显的是那些驻留在脊髓中的神经元。目前，我们还没有很好地掌握脊髓神经元是如何控制运动的。作为渥太华大学生物系的一名新研究员，我正在建立一个综合的、多学科的研究计划，其长期目标是确定神经元在产生运动中所扮演的角色，以及它们的神经元活动如何无缝地结合在一起，以适当地控制运动。*斑马鱼是一种新兴的动物模型，已经被用来更好地了解水生物种中的游泳和陆地动物的地面运动。斑马鱼神经系统运作的基本原理已被证明在进化上在其他脊椎动物如哺乳动物中是保守的，因为在两栖动物和哺乳动物中存在具有类似功能的神经元。斑马鱼具有独特的特征，如其幼体的透明度和许多遗传工具的可获得性，这使其成为研究运动的神经控制的理想选择。我这项提议的目标是了解脊髓神经元是如何产生游泳的，我将利用斑马鱼的特征来实现这一点。我的研究小组将通过神经记录来确定脊髓神经元的活动频率。这种活动频率将与推动斑马鱼的身体振荡相关。我们还将使用一种新技术，在鱼游泳时，我们可以选择性地操纵脊髓神经元的神经元活动。通过透过透明斑马鱼幼体的皮肤照射，我们可以操纵经过基因改造的神经元对光做出反应的神经元活动。这使我们能够确定在游泳过程中操纵神经元的活动将如何改变整条鱼的游泳模式。作为这些研究方法的结果，我们将独一无二地确定哪些神经元负责游泳的基本特征，如设置身体振荡的频率，将这些振荡从头传播到尾，以及协调身体的左右两侧。*鉴于斑马鱼和人类神经系统之间的相似之处，我们的研究将提高我们对神经系统如何在人类体内协调运动的理解。这项提议将建立一个神经生物学研究计划，培训年轻的研究人员在新兴动物模型中应用尖端技术。此外，我们的发现还可以应用于呼吸、睡眠-觉醒周期和认知等基本神经节律的研究。*

***The nervous system ensures that we move properly. In order to do so, the nervous system must set the pace at which we move, coordinate all of our muscles so that they act in an organized manner, and ensure that the right and the left side of our body work in tandem. These tasks are accomplished by neurons, most notably those residing in the spinal cord. At present, we do not have a good grasp as to how spinal neurons operate to control movement. As a new investigator in the Department of Biology, University of Ottawa, I am establishing an integrative and multidisciplinary research program whose long-term goal is to determine the roles played by neurons in generating movement and how their neuronal activity meshes seamlessly to properly control movement.***The zebrafish is an emerging animal model that has been used to gain a better understanding of swimming in aquatic species and over-ground locomotion in terrestrial animals. Fundamental principles by which the nervous system operates in zebrafish have been shown to be evolutionarily conserved in other vertebrates such as mammals due to the presence of neurons that have analogs in amphibians and mammals. Zebrafish have unique features such as the transparency of their larvae and the availability of many genetic tools that make it ideal for studying the neural control of movement. My objective for this proposal is to understand how swimming is generated by neurons in the spinal cord and I will exploit features of zebrafish to accomplish this. My research group will determine the frequency of activity of spinal neurons through neural recordings. This frequency of activity will be correlated to that of body oscillations that propel zebrafish. We will also use a novel technique where we can selective manipulate neuronal activity of spinal neurons while fish are swimming. By shining light through the skin of transparent zebrafish larvae, we can manipulate the neuronal activity of neurons genetically modified to respond to light. This allows us to determine how manipulating the activity of neurons during swimming will modify the swimming patterns of the whole fish. As a consequence of these research approaches, we will be uniquely positioned to determine which neurons are responsible for fundamental features of swimming such as setting the frequency of body oscillations, for propagating these oscillations from head to tail, and for coordinating the left and right side of the body. ***Given the similarities between zebrafish and humans nervous systems, our studies will improve our understanding of how the nervous system functions to coordinate movement in humans. This proposal will establish a program of neurobiological research that will train young researchers to employ cutting-edge techniques in an emerging animal model. In addition, our findings can be applied to the study of fundamental neural rhythms involved in breathing, sleep-wake cycles and cognition, amongst others. *** *** **