Dissecting the structure and function of vertebrate sensorimotor neural circuits using larval zebrafish

我们日常生活中至关重要的是能够使用感官信息来计划和产生目标导向的运动。这些行为包括基本任务，例如伸手去拿物体或走上一段楼梯。尽管这些行为相对简单，但控制它们的所谓“感觉运动神经回路”却极其复杂。确定感觉和运动背后的这些回路的结构和功能对于理解大脑如何产生行为至关重要。神经科学家在解开回路功能时面临的一些挑战是哺乳动物大脑中神经元的数量及其令人难以置信的多样性。此外，大脑的规模和不透明度阻碍了我们彻底记录行为过程中神经元活动的能力。分子生物学、显微镜和计算领域的最新技术进步使得克服其中一些实验障碍成为可能。这些进步为研究人员提供了前所未有的机会，可以对神经回路的运作方式做出根本性的发现。 我的实验室将采用综合的多学科方法，以斑马鱼幼虫为模型来了解感觉运动回路的功能。斑马鱼幼体因其无与伦比的实验方法组合而成为研究神经回路的极其强大的系统，特别是全面监测和操纵整个大脑活动的独特能力。我们将利用这些方法来确定鱼的回路如何使用视觉信息来控制两种目标导向的行为：捕获猎物和躲避捕食者。具体来说，我们将重点揭示鱼的感觉运动回路是否在特定行为中发挥专用作用，或者在不同行为中更广泛地使用。我们将在脊椎动物中高度保守的三个大脑结构中提出这个问题，它们代表涉及感觉处理、运动选择和运动产生的电路。从这项研究中获得的知识将对我们如何理解脊椎动物行为背后的大脑神经处理产生重大影响。感觉运动回路功能的发现也将对新脑机接口的开发产生影响，这种接口将允许仅通过思考运动来轻松控制假肢。最后，该研究项目有可能提供见解，指导开发强大的计算机技术，这些技术植根于感官处理和运动产生的进化解决方案。

Essential to our daily lives is the ability to use sensory information to plan and produce goal-directed movements. Such behaviours include basic tasks like reaching for an object or walking up a flight of stairs. Despite the relative simplicity of these behaviours, there is an astounding amount of complexity in the so-called “sensorimotor neural circuits” that control them. Determining the structure and function of these circuits that underlie sensation and movement is essential to understanding how the brain produces behaviour. Some of the challenges faced by neuroscientists in unraveling circuit function are the sheer number of neurons in the mammalian brain and their incredible diversity. Additionally, the scale and opacity of the brain hinders our ability to thoroughly record neuronal activity during behaviour. Recent technological advances in molecular biology, microscopy and computing have made it possible to begin to overcome some of these experimental hurdles. These advances present researchers with an unprecedented opportunity to make fundamental discoveries about how neural circuits operate. My laboratory will take an integrated and multidisciplinary approach to understand how sensorimotor circuits function using the larval zebrafish as a model. The larval zebrafish has emerged as an extremely powerful system to study neural circuits due to its unparalleled combination of experimental approaches, notably the exclusive ability to comprehensively monitor and manipulate activity throughout the brain. We will utilize these approaches to determine how circuits in the fish use visual information to control two goal-directed behaviours, prey capture and predator avoidance. Specifically, we will focus on uncovering whether sensorimotor circuits in the fish have dedicated roles in a particular behaviour or are used more generally across different behaviours. We will ask this question in three brain structures that are highly conserved across vertebrates and represent circuitry involved in sensory processing, movement selection and movement production. Knowledge gained from this research will have a significant impact on how we understand the neural processing in the brain that underlies vertebrate behaviour. Discoveries in sensorimotor circuit function will also have implications for the development of new brain-machine interfaces that will allow for the effortless control of prosthetic limbs simply by thinking about movements. Lastly, this research program has the potential to provide insights that will guide the development of powerful in silico technologies rooted in evolution's solutions to sensory processing and movement production.