Development and Divergence of Whole-Brain Activity

项目摘要/摘要 动物的大脑由相互连接的神经元组成，这些神经元负责处理 许多时间标尺来指导行为。大脑功能部分由动物的连接体决定 -它大脑中每个连接的拓扑、强度和价态。而整个连接体的草稿 一种动物(线虫秀丽线虫)已经存在几十年了，最近的研究发现 不同发育阶段和不同个体之间的连接体差异很大。它并不像预期的那样刻板印象。 我们不知道这种连通性的巨大差异是如何通过发育在大脑活动中表现出来的 或者在个人之间。尽管如此，动物拥有的单一连接体必须以某种方式支持 动物在给定瞬间可能表现出的每一种行为。这些行为中的每一种都可能发生重叠 大脑的一部分。 该项目旨在利用钙成像来研究线虫的全脑活动如何通过 发展和个人之间的关系。我们的目标是准确地阐明大规模的结构和功能 在一个简单的系统中是相关的。为了做到这一点，我们将以细胞分辨率在一个 从刚孵化的幼虫经过一系列蜕皮过程中表现良好的个体动物的集合 然后长大成人。这些长期的钙记录将得到微流体测量的补充。 不同发育阶段的全脑对化学感觉线索的反应。在整个过程中，我们 将集中讨论以下大问题：(1)蠕虫中每个神经元的活动是如何通过 发育？(2)基因相同的个体之间大脑活动有何不同？(3)每个人的大脑活动情况如何？ 上述问题受环境背景变化的影响？(4)大脑与大脑的关系如何 活动和连通性会随着发展而变化，不同的人之间会有什么不同？ 如果成功，这项工作可以提供前所未有的洞察力，让人们了解动物大脑功能的变化 增加神经元、连接和突触。它将展示个体间和个体内的差异是如何 与大脑的连接体有关。这将对指导人们对大脑活动的预期产生直接的价值 在其他模型系统和人类中，大脑连接也是相关的，那里关于连接的直接信息较少 现成的。

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.