Dissecting the Fabric of the Cerebral Cortex

描述 摘要： 大脑皮层容纳我们的心理功能，如感知，认知和行动。尽管在发现单细胞和分子水平过程的特性方面取得了重大进展，但我们仍然不知道皮层在电路水平上如何工作。这个问题的本质在于理解数十亿个神经元如何通过数万亿个连接进行通信，协调它们的活动，从而产生我们的心理能力。我们还远远不能同时测量所有无数皮层细胞的活动，并组装它们的物理布线图（连接体）。然而，如果存在着支配这种复杂性的基本原则和规则，那么发现这些原则就为理解大脑皮层的功能提供了一个显而易见的策略。事实上，已经假设皮层是由基本的信息处理模块组成的。近世纪来，解剖学家们已经观察到皮质微结构的显著规律性：来自共同祖细胞的细胞串具有突触连接的倾向，排列成与皮质表面垂直的小圆柱。这些微柱被假设为皮层电路的基本功能单位。如果人们能够理解它们的组织原理，那么理解大脑皮层如何工作的任务就会大大简化。发现这些基本模块的功能就像发现基因一样，最终导致了世纪的分子革命。到目前为止，由于技术限制，这些结构无法详细研究。为了了解微柱的功能，必须同时监测其所有组成神经元的体内活动。我们的目标是克服这些技术挑战，并开发研究整个微腔的体内方法。我们建议开发基于3D随机访问的体内显微镜

DESCRIPTION Abstract: The cerebral cortex houses our mental functions like perception, cognition and action. Despite major advances in discovering the properties of single cells and molecular-level processes, we still do not know how the cortex works at the circuit level. The essence of the problem lies in understanding how the billions of neurons communicating through trillions of connections orchestrate their activities to give rise to our mental faculties. We are far from being able to simultaneously measure the activity of all the myriads of cortical cells and assemble their physical wiring diagram (connectome). However, if there are underlying principles and rules that govern this complexity, discovering these principles provides an obvious strategy for understanding how the cortex functions. Indeed, it has been hypothesized that the cortex is composed of elementary information processing modules. For almost a century anatomists have observed remarkable regularity in the cortical microarchitecture: strings of cells derived from a common progenitor cell and having a propensity of being synaptically connected are arranged to form small columns orthogonal to the cortical surface. These microcolumns are hypothesized to be the elementary functional units of cortical circuitry. If one were able to understand their organizing principles, the task of understanding how the cortex works would be simplified immensely. Discovering the function of these elementary modules would be analogous to the discovery of the gene, which ultimately led to the molecular revolution of the 20th century. So far, these structures could not be studied in detail due to technical limitations. To understand the function of a microcolumn, it is imperative to simultaneously monitor the activity of all its constituting neurons in vivo. It is our goal to overcome these technical challenges and develop in-vivo methods to study an entire microlumn. We propose to develop in vivo microscopy based on 3D random-access