Viral Strategies for Functional Connectomics in the Visual System

视觉系统中功能性连接组学的病毒策略

• 批准号: 9751980
• 负责人: R CLAY REID
• 金额: $ 90.28万
• 依托单位: ALLEN INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751980
• 关键词: Address; Alzheimer' s Disease; Anatomy; Anterolateral; Area; Array tomography; Back; Brain; Brain Diseases; Calcium; Cells; Cerebral cortex; Consensus; Data; Dendrites; Electron Microscopy; Epilepsy; Feedback; Foundations; Functional Imaging; Functional disorder; Generations; Glycoproteins; Image; Interneurons; Label; Lasers; Lateral; Link; Location; Logic; Mental disorders; Methods; Mind; Modeling; Motor; Neurons; Neurosciences; Output; Pattern; Physiological; Physiology; Polymerase Gene; Process; Property; Public Health; Pyramidal Cells; Rabies; Rabies virus; Recurrence; Resolution; Scanning; Sensory; Signal Transduction; Stimulus; Stroke; Synapses; Techniques; Testing; Tracer; Transgenes; V1 neuron; Variant; Viral; Virus; Visual Cortex; Visual system structure; Work; anatomical tracing; area V1; area striata; autism spectrum disorder; brain cell; calcium indicator; cognitive function; cytotoxicity; exhaustion; experimental study; extrastriate visual cortex; hippocampal pyramidal neuron; improved; in vivo; information processing; mouse model; movie; nervous system disorder; novel strategies; postsynaptic; postsynaptic neurons; presynaptic; receptive field; response; sensory cortex; tool; two photon microscopy; two-photon; virtual; visual stimulus

Project Summary / Abstract A fundamental but unsolved question in neuroscience is how specific connections between brain cells (neurons) underlie information processing. Circuits in the cerebral cortex—the part of the mammalian brain that underlies high-level sensory, motor, and cognitive function—consists of tens of thousands of neurons, each of which sends and receives thousands of connections. Perhaps the biggest reason we don't understand the cerebral cortex is that we don't have an actual wiring diagram of any single cortical circuit. But even if we had a wiring diagram, we would need to know what each neuron in a circuit is doing: its physiology. In this proposal, we plan study the functional logic of networks in the visual cortex by examining groups of connected neurons whose responses to visual stimuli have been characterized. We will combine two techniques to tackle this difficult problem. Connections between neurons will be determined with a modified virus that allows us to specifically labels ensembles of neurons, all of which connect with a single 'target' neuron in each experiment. Once the neurons are labeled, we will use an advanced form of scanning-laser imaging (calcium imaging with two-photon microscopy) that allows us to make movies of each neuron's activity in response to carefully chosen visual stimuli. Together, these tools will allow to probe the functional logic of cortical circuits: the relationship between neuronal function and the wiring between neurons. The cerebral cortex is a network of networks. There are many different cortical regions each of which has its distinct inputs and outputs and distinct physiological properties. For instance, roughly ten visual cortical areas process different aspects of visual stimuli. We will start by studying the functional logic of wiring within three visual cortical areas: V1, AL and PM. We will then examine the functional logic of connections between these areas. The viral strategy that we employ is currently the only method that allow for both local and inter- areal connection to be studied along with physiology. The data we collect will help us understand feedforward, lateral, and feedback connections in cortical circuits and will form the foundation of new, data-driven models of cortical function.

项目概要/摘要 神经科学中一个基本但尚未解决的问题是脑细胞之间的特定连接如何 （神经元）是信息处理的基础。大脑皮层中的电路——哺乳动物大脑的一部分 它是高级感觉、运动和认知功能的基础——由数以万计的神经元组成， 每个都发送和接收数千个连接。也许我们不明白的最大原因 大脑皮层的问题是我们没有任何单个皮层电路的实际接线图。但即使我们 有了接线图，我们需要知道电路中的每个神经元正在做什么：它的生理学。在这个 建议，我们计划通过检查连接的组来研究视觉皮层网络的功能逻辑 对视觉刺激的反应已被表征的神经元。 我们将结合两种技术来解决这个难题。神经元之间的连接将是 用经过修改的病毒确定，该病毒使我们能够专门标记神经元集合，所有这些 在每个实验中与单个“目标”神经元连接。一旦神经元被标记，我们将使用 先进的扫描激光成像（双光子显微镜钙成像）使我们能够 制作每个神经元响应精心选择的视觉刺激的活动的电影。这些工具一起 将允许探索皮质回路的功能逻辑：神经元功能和 神经元之间的布线。 大脑皮层是一个由网络组成的网络。有许多不同的皮质区域，每个区域 具有独特的输入和输出以及独特的生理特性。例如，大约十个视觉皮层 区域处理视觉刺激的不同方面。我们将从研究内部接线的功能逻辑开始 三个视觉皮层区域：V1、AL 和 PM。然后我们将检查之间连接的功能逻辑 这些领域。我们采用的病毒式传播策略是目前唯一能够同时实现本地和国际传播的方法。 区域连接与生理学一起研究。我们收集的数据将帮助我们理解前馈， 皮质回路中的横向和反馈连接将构成新的数据驱动模型的基础 皮质功能。