Viral Strategies for Functional Connectomics in the Visual System

项目摘要/摘要 神经科学中一个基本但尚未解决的问题是，脑细胞之间的具体联系是如何 (神经元)是信息处理的基础。大脑皮层中的回路--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--由数万个神经元组成， 其中每一个都发送和接收数千个连接。也许我们不理解的最大原因 大脑皮层是，我们没有任何单一皮质回路的实际接线图。但即使我们 有了接线图，我们就需要知道电路中的每个神经元都在做什么：它的生理学。在这 建议，我们计划通过检查连接的组来研究视觉皮质中网络的功能逻辑 神经元对视觉刺激的反应已经被描述。 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 由一种改良的病毒确定，这种病毒允许我们专门标记神经元集合，所有这些 在每个实验中连接一个“目标”神经元。一旦神经元被标记，我们将使用 先进形式的扫描-激光成像(双光子显微镜钙成像)，使我们能够 拍摄每个神经元对精心挑选的视觉刺激做出反应的活动。总而言之，这些工具 将允许探索皮层回路的功能逻辑：神经元功能与 神经元之间的连接。 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 有其不同的输入和输出以及不同的生理特性。例如，大约10个视觉皮质 区域处理视觉刺激的不同方面。我们将从研究内部布线的功能逻辑开始 三个视觉皮质区域：V1、AL和PM然后，我们将检查功能逻辑之间的联系 这些区域。我们采用的病毒策略是目前唯一同时允许局部和跨区域的方法 区域联系将与生理学一起研究。我们收集的数据将帮助我们理解前馈， 皮质回路中的侧向连接和反馈连接，将构成新的数据驱动模型的基础 大脑皮层功能。

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.