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.

项目摘要 /摘要 神经科学中的基本但未解决的问题是脑细胞之间的特定联系 （神经元）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 这是高级感觉，运动和认知功能的基础，这是成千上万的神经元的一致主义者 每个连接都会发送并接收数千个连接。也许我们不了解的最大原因 大脑皮层是我们没有任何单个皮质电路的实际接线图。但是即使我们 有了一个接线图，我们需要知道电路中的每个神经元在做什么：其生理学。在这个 提案，我们通过检查连接的组来计划研究视觉皮层中网络的功能逻辑 对视觉刺激的反应的神经元已被表征。 我们将结合两种解决这个困难问题的技术。神经元之间的联系将是 用修饰的病毒确定，使我们能够专门标记神经元的集合，所有这些 在每个实验中与单个“靶”神经元连接。一旦标记了神经元，我们将使用 扫描激光成像的高级形式（具有两光子显微镜的钙成像），使我们能够 制作每个神经元活动的电影，以仔细选择视觉刺激。在一起，这些工具 将允许探测皮质电路的功能逻辑：神经元功能与 神经元之间的接线。 大脑皮层是网络网络。每个不同的皮质区域每个区域 具有独特的输入和输出以及不同的物理特性。例如，大约十个视觉皮质 区域处理视觉刺激的不同方面。我们将首先研究内部接线的功能逻辑 三个视觉皮质区域：V1，AL和PM。然后，我们将检查连接的功能逻辑 这些区域。我们员工的病毒策略目前是唯一允许本地和间的方法 与生理学一起研究的方案。我们收集的数据将帮助我们了解进料， 横向和皮质电路中的反馈连接，将构成新的，数据驱动的模型的基础 皮质功能。