Understanding the microcircuits in monkey sensory cortices: a connectomic approach

摘要 共聚焦和电子显微镜（EM）的系列化以及自动成像的发展 分割使我们能够阐明皮层回路的一些结构细节， 细胞和突触水平。这一信息是至关重要的，因为有一个密切的联系， 不同脑区回路的形态特征及其功能。人们普遍认为， 皮层的典型微电路是跨皮层的重复基序。一旦结构和 在局部基序中的功能被理解为这可以应用于所有的皮质。然而，最近， 已经表明，有主要的层流，地区和物种的差异，需要考虑到 根据这个模型。感觉区典型回路的另一个重要特征是， 最初的丘脑皮层（TC）驱动输入到皮层中的第4层，这被认为是弱的，需要 被大量放大以获得观察到的加标率。然而，最近的研究表明， 弱TC假设，低估了TC强度2-4倍。我假设， 虽然典型回路可以为皮层回路功能提供一般框架，但不同的 感觉脑区在它们的神经元和突触分布中具有主要的层状差异。这些 这些差异反过来又反映了大脑区域不同的处理角色和能力。测试 这个假设，我将研究三个主要的感觉区在猕猴皮层使用聚焦 离子束/扫描EM，使用高分辨率共聚焦显微镜确定详细的突触连接 显微镜，以提供特定突触连接的大规模测定，并使用中- 分辨率共聚焦显微镜来确定特定脑区域中的总体细胞类型分布。如果像 我假设，地区之间存在着主要的数量差异，这将反映他们的多样性。 处理角色和能力，这将要求规范电路的概念的细化。 这些定量结果对于建立真实的基于群体的皮层尖峰发放模型是重要的， 可以重现大脑中发现的许多详细的功能特征。他们也是 重要的是，了解正常大脑的基本皮层组织是必不可少的，因为它 提供了一个标准，根据这个标准可以判断哪些过程可以被视为被改变， 在影响大脑皮层的疾病中受损。此外，这个项目的一个重要组成部分是我的 作为PI的专业发展。因此，我制定了一项研究增强计划， 增加我的研究奖学金和出版物，最终目标是获得非SCORE 研究支持。

Abstract The development of serial confocal and electron-microscopy (EM), and automated image segmentation have allowed us to elucidate some of the structural details of the cortical circuit at the cellular and synaptic level. This information is critical because there is a close link between the morphological properties of circuits in different brain areas and their function. It is broadly accepted that the canonical microcircuit of the cortex is a repeating motif across cortex. Once the structure and function in the local motif is understood this could be applied across all of cortex. However, recently it has been shown that there are major laminar, areal and species differences that need to be taken into account by this model. Another important feature of the canonical circuit in sensory areas is that the initial thalamocortical (TC) driving input to layer 4 in cortex, which was presumed to be weak, needs to be massively amplified to obtain the observed rates of spiking. However, recent studies have shown that the weak TC assumption, has underestimated the TC strength by 2-4 times. I hypothesis that, although the canonical circuit may provide general framework for cortical circuit functioning, diverse sensory brain areas have major laminar differences in their neuronal and synaptic distributions. These differences will, in turn, reflect the diverse processing roles and capabilities of the brain areas. To test this hypothesis I will examine three primary sensory areas in macaque monkey cortex using Focused Ion Beam/Scanning EM to determine detailed synaptic connectivity, using high-resolution confocal microscopy to provide large scale determination of specific synaptic connectivity, and using mid- resolution confocal microscopy to determine global cell type distributions in specific brain regions. If, as I hypothesize, there are major quantitative differences between areas that will reflect their diverse processing roles and capabilities, this will call for a refinement of the concept of the canonical circuit. These quantitative results are important to build realistic population based spiking models of cortex that can reproduce many of the detailed functional characteristics that are found in the brain. They are also important because understanding the basic cortical organization of the normal brain is essential, as it provides the standard against which it can be judged which processes can be seen to be altered or damaged in disorders that affect the cerebral cortex. Additionally, an important part of this project is my professional development as a PI. As such, I have established a research enhancement plan to increase my research scholarship and publications, with the final goal of acquiring non-SCORE research support.