Dissecting the Fabric of the Cerebral Cortex

描述 摘要： 大脑皮层容纳了我们的心理功能，如感知、认知和行动。尽管在发现单细胞的特性和分子水平的过程方面取得了重大进展，但我们仍然不知道皮质在电路水平上是如何工作的。问题的实质在于理解通过数万亿连接进行交流的数十亿个神经元是如何协调它们的活动来产生我们的智力的。我们还远不能同时测量所有无数皮质细胞的活动，并组装它们的物理接线图(连接体)。然而，如果存在支配这种复杂性的潜在原则和规则，那么发现这些原则将为理解大脑皮层如何发挥作用提供一个显而易见的策略。事实上，人们假设大脑皮质是由基本的信息处理模块组成的。近一个世纪以来，解剖学家观察到了大脑皮层微结构中显著的规律性：从一个共同的祖细胞衍生出来的具有突触连接倾向的一串串细胞排列成与大脑皮层表面垂直的小柱。这些微柱被假设为皮质回路的基本功能单位。如果一个人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类似于基因的发现，基因的发现最终导致了20世纪的分子革命。到目前为止，由于技术上的限制，这些结构还不能被详细研究。为了了解微柱的功能，必须同时监测体内所有构成微柱的神经元的活动。我们的目标是克服这些技术挑战，开发体内方法来研究整个微瘤。我们建议发展基于3D随机存取的活体显微镜

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