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大和发展，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秀丽隐杆线虫从出生到成年的大脑和行为，秀丽隐杆线虫是一种重要的和广泛研究的神经科学模型。研究人员将创造一个受控的环境，在这里，每只动物从出生、自由活动到长大成人，同时用显微镜连续扫描蠕虫神经系统中每个神经元的活动模式。由于它们成熟迅速（2天），神经系统小（302个神经元），这项技术将用于回答有关大脑发育的基本问题。例如，高度保守的行为模式，如向前和反向运动，是如何从神经系统中产生的，以适应从出生到成年增长十倍的身体？协调大脑、身体和行为的平行发展是所有动物都面临的问题。秀丽隐杆线虫的可及性将产生任何动物大脑和行为发育的第一个综合测量。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之间丰富的界面上工作。研究人员将开发一个系统——一个电动的、旋转的琼脂球——在这个系统上，线虫可以不受干扰地自由移动，从进食、生长、蜕皮到成年，共经历四个幼虫阶段。在线虫的整个生命过程中，该系统将记录整个神经系统的活动，通过其光学透明的身体可视化使用共聚焦显微镜，实现视频速率的体积记录。这些实验将提供前所未有的数据集，描述个体动物的行为生活史与整个大脑活动模式的时间相关性。将这些丰富的数据集在野生型动物和信息突变体之间进行比较，将允许对神经发育、调节、学习和记忆中广泛的相互关联和共享过程进行解剖。例如，了解运动回路的发育过程将通过获得电路范围的测量来实现，这些测量描述了驱动0.1毫米长的幼年蠕虫向前和向后运动的20个神经元运动回路如何扩展到驱动1毫米长的成年蠕虫相同运动的80个神经元运动回路。这些研究将阐明神经系统的全系统变化，因为它动态地跟上动物的生长。

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.