Coding and wiring in a million cortical neurons

该项目将揭示小鼠视觉皮层所有区域的大量神经元的集体功能，通过将我们完善的先进技术与变革性的新成像方法相结合。大脑皮层的功能是由无数神经元的集体活动组织起来的，这些神经元的联合活动构成了一个我们只能以片段形式阅读的代码。揭示这种代码和支持它的线路的关键是能够记录跨皮层区域的大量单个神经元。这是现在可能感谢光珠显微镜（LBM），它允许前所未有的记录约100万皮质神经元。首先，我们将使用LBM来表征视觉皮层所有区域的神经元联合活动所使用的代码。我们将在小鼠在虚拟现实中观看图像、跑步和导航时，对所有视觉区域的约100万个神经元的活动进行成像。因此，我们将测试关于视觉区域的视觉代码的关键假设，以及与行为，大脑状态和导航相关的内部信号的影响。其次，我们将揭示支持这种神经代码的线路。我们将LBM成像与我们实验室建立的狂犬病追踪技术配对，并将一个神经元的反应与所有视觉区域的突触前神经元的反应联系起来。因此，我们将测试前馈和反馈连接的布线假设，这些连接决定视觉反应，并携带与行为，大脑状态和导航相关的内部信号。最后，我们将探索一个皮层神经元的反应是如何从它接收的数千个突触中产生的。我们将使用更高分辨率的LBM来成像神经元的完整树突树，并使用狂犬病追踪来成像与之相连的突触，从而揭示与视觉、行为和导航相关的信号的突触组织，并通过树状结构来测试它们的因果作用。结果将提供前所未有的数据，揭示大脑皮层主要部分的编码和布线活动，为皮层功能的基本理论提供实验测试。

This project will reveal the collective function of vast populations of neurons across all areas of the mouse visual cortex, by combining advanced techniques that we perfected with a transformational new imaging method. Cortical function is organized by the collective firing of a myriad neurons, whose joint activity constitutes a code that we have been able to read only in fragments. Key to revealing this code and the wiring that supports it, is the ability to record from vast populations of individual neurons across cortical areas. This is now possible thanks to the Light Beads Microscope (LBM), which allows unprecedented recordings from ~1 million cortical neurons. First, we will use the LBM to characterize the code used by the joint activity of neurons across all areas of the visual cortex. We will image the activity of ~1 million neurons across all visual areas while mice view images, run, and navigate in virtual reality. We will thus test key hypotheses about the visual code across visual areas, and about the influence of internal signals related to behavior, brain state, and navigation. Second, we will reveal the wiring that supports this neural code. We will pair LBM imaging with rabies tracing techniques established in our laboratory, and relate the responses of one neuron to those of its presynaptic neurons across all visual areas. We will thus test hypotheses on the wiring of feedforward and feedback connections that determine visual responses and that carry internal signals related to behavior, brain state, and navigation. Finally, we will explore how the responses of one cortical neuron arise from the thousands of synapses that it receives. We will use the LBM at higher resolution to image a neuron's full dendritic tree and use rabies tracing to image the synapses that connect to it. We will thus reveal the synaptic organization of signals related to vision, behavior, and navigation, and test their causal role through dendrotomies. The results will deliver unprecedented data that will reveal the coding and wiring underlying activity in a major portion of the cerebral cortex, providing an experimental test of fundamental theories of cortical function.