BRAIN EAGER: Functional dynamics of whole brain activity, behavior, and development from birth to adulthood

从出生到成年，大脑和神经系统不断扩张和发育，以跟上不断增长的身体。任何动物，包括人类，都必须不断地增加或改变神经元和连接，以获得新的行为或保留旧的行为。该项目旨在开发和应用技术来监测线虫从出生到成年期的大脑和行为，线虫是神经科学中一个重要的、被广泛研究的模型。当显微镜连续扫描蠕虫神经系统中每一个神经元的活动模式时，将创造一个受控的环境，在那里个体动物出生、自由漫步并成长到成年。由于它们的快速成熟(2天)和小神经系统(302个神经元)，这项技术将被用来回答关于发育中的大脑的基本问题。例如，高度保守的行为模式，如向前和向后运动，是如何从神经系统适应从出生到成年增长十倍的身体的？协调大脑、身体和行为的并行发展是所有动物都面临的问题。线虫的可及性将首次对任何动物的大脑和行为发育进行全面测量。将发育生物学、神经生理学和神经技术结合起来，将培养年轻的科学家，他们将在物理科学和生命科学的丰富界面上工作。将开发一种系统--一种电动的、旋转的琼脂涂层球--线虫可以在其上自由移动，在其上觅食、生长、蜕皮、经历四个幼虫阶段，然后成为成虫。在线虫的整个生命过程中，该系统将使用实现视频率体积记录的共焦显微镜来记录整个神经系统的活动，整个神经系统在其光学透明的身体上可视化。这些实验将提供前所未有的数据集，描述单个动物的行为生活史，并与整个大脑活动模式进行时间关联。对野生动物和信息丰富的突变体之间的这些丰富的数据集进行比较，将允许剖析神经发育、调节、学习和记忆中广泛的相互关联和共享的过程。例如，通过获得电路范围的测量，描述驱动0.1毫米长的幼虫向前和向后运动的20个神经元的马达电路如何扩展为驱动1毫米长的成虫的相同运动的80个神经元的马达电路，就可以理解马达电路的发育进程。这些研究将阐明神经系统在整个系统内的变化，因为它动态地与动物的生长保持同步。

From birth to adulthood, the brain and nervous system continuously expand and develop to keep up with the growing body. Neurons and connections must constantly be added or changed for any animal, including humans, to gain new behaviors or retain old ones. This project is to develop and apply technology to monitor brain and behavior from birth to adulthood of the roundworm C. elegans, an important and widely studied model for neuroscience. A controlled environment will be created where individual animals are born, roam freely, and grow to adulthood while a microscope continuously scans the activity patterns of every neuron in the worm's nervous system. Because of their rapid maturation (2 days) and small nervous system (302 neurons), the technology will be used to answer fundamental questions about the developing brain. For example, how do highly conserved behavioral patterns like forward and reverse movement emerge from a nervous system that adapts to a body that grows ten-fold from birth to adult? Coordinating the parallel development of brain, body, and behavior is a problem faced by all animals. The accessibility of C. elegans will yield the first comprehensive measurements of brain and behavior development in any animal. Bringing together developmental biology, neurophysiology, and neurotechnology will train young scientists who will work at the rich interface between the physical and life sciences.A system will be developed-- a motorized, rotating agar-coated ball-- upon which a nematode can freely move without interruption as it feeds, grows, molts through four larval stages, and becomes an adult. Throughout the nematode's life, the system will record the activity of the entire nervous system visualized throughout its optically transparent body using a confocal microscope that achieves video-rate volumetric recording. These experiments will provide unprecedented datasets that describe the behavioral life history of an individual animal in temporal correlation with whole brain activity patterns. Comparison of these rich datasets between wild-type animals and informative mutants will allow dissection of a wide range of interconnected and shared processes in neurodevelopment, regulation, learning, and memory. For example, understanding the developmental progression of the motor circuit will be achieved by obtaining circuit-wide measurements that describe how the 20-neuron motor circuit that drives the forward and backward movements of the 0.1-mm long juvenile worm is expanded into the 80-neuron motor circuit that drives the same movements of the 1-mm long adult. These studies will illuminate system-wide changes in the nervous system as it dynamically keeps up with animal growth.