Development and Divergence of Whole-Brain Activity

项目总结/摘要 动物的大脑由相互连接的神经元组成，负责处理感官信息， 许多时间尺度来指导行为。大脑的功能部分由动物的连接体决定 - 它大脑中每一个连接的拓扑结构强度和效价而整个连接体的草图 一种动物（秀丽隐杆线虫）已经存在了几十年，最近的研究发现， 连接体在发育过程中和个体之间变化很大。它并不像预期的那样刻板。 我们不知道这种连接的巨大变化如何通过发育在大脑活动中表现出来 或个体之间。尽管如此，动物的单个连接体必须以某种方式能够支持 动物在特定时刻的所有行为。这些行为中的每一个都可能涉及重叠 大脑的一部分。 这个项目旨在利用钙成像来研究C。elegans通过 发展和个人之间。我们的目标是明确大规模的结构和功能 在一个简单的系统中相互关联。为了做到这一点，我们将进行全脑成像与细胞分辨率在一个 从刚孵出的幼虫到一系列的蜕皮过程中表现良好的个体动物的集合 变成成年人这些长期的钙记录将通过微流体测量来补充 在多个发育阶段对化学感觉线索的全脑反应。在整个过程中，我们 我将集中研究以下几个大问题：（1）蠕虫中每个神经元的活动是如何通过 发展？(2)在基因相同的个体之间，大脑活动是如何变化的？(3)每个人如何 上述问题受环境背景变化的影响？(4)大脑和大脑之间的关系 活动和连通性在发展过程中发生变化，个体之间又有何不同？ 如果成功的话，这项工作将为动物大脑功能的变化提供前所未有的见解。 增加了神经元、连接和突触。它将显示个体间和个体内的变异是如何 与大脑的连接体有关。这将对指导人们对大脑活动的预期有直接的价值。 和大脑线路在其他模型系统和人类中是相关的，其中关于线路的直接信息较少 随时可用。

Project Summary/Abstract An animal’s brain consists of interconnected neurons that are responsible for processing sensory information over many timescales to guide behavior. The function of that brain is determined partially by the animal’s connectome – the topology, strength, and valence of every connection in its brain. While a draft of the whole connectome for an animal (the worm Caenorhabditis elegans) has been available for decades, recent work has found that this connectome varies dramatically through development and between individuals. It is not stereotyped as expected. We do not know how this large variability in connectivity manifests itself in brain activity through development or between individuals. Nonetheless, the single connectome an animal has must somehow be able to support every behavior that the animal may perform in a given instant. Each of these behaviors may engage overlapping portions of the brain. This project aims to leverage calcium imaging to study how whole-brain activity in C. elegans varies through development and between individuals. Our goal is to clarify precisely how large-scale structure and function are related in a simple system. To do this, we will perform whole-brain imaging with cellular resolution in a collection of behaving individual animals as they progress from newly-hatched larvae through a series of molts and turn into adults. These long-term calcium recordings will be complemented by microfluidic measurements of whole-brain responses to chemosensory cues at multiple developmental stages. Throughout this process, we will focus on the following big questions: (1) How does the activity of every neuron in a worm change through development? (2) How does brain activity vary between genetically identical individuals? (3) How are each of the above questions affected by changes in environmental context? (4) How does the relationship between brain activity and connectivity change over development, and how does it vary between individuals? If successful, this work could provide unprecedented insight into how brain function changes as an animal adds neurons, connections, and synapses. It will show how inter-individual and intra-individual variation are related to the brain’s connectome. This will have immediate value in guiding expectations about how brain activity and brain wiring are related in other model systems and humans, where direct information about wiring is less readily available.