Understanding the microcircuits in monkey sensory cortices: a connectomic approach

摘要 系列共聚焦电子显微镜(EM)和自动成像的发展 分段使我们能够阐明大脑皮质环路的一些结构细节 细胞和突触水平。这一信息非常关键，因为 不同脑区回路的形态特征及其功能。人们普遍认为 大脑皮层的典型微回路是一个贯穿大脑皮层的重复的主题。一旦结构和 在局部基序中的功能被理解，这可以应用于所有的皮质。不过，最近它 已经表明，存在主要的层流、区域和物种差异，需要考虑 按此模型记账。感觉区正则回路的另一个重要特征是 最初的丘脑皮质(TC)驱动输入到皮质的第四层，这被认为是弱的，需要 被大规模放大，以获得观察到的尖峰速度。然而，最近的研究表明， 弱热带气旋的假设，将热带气旋的强度低估了2-4倍。我假设， 尽管正则回路可以提供大脑皮层回路功能的一般框架，但也是多样的 感觉脑区在神经元和突触的分布上有很大的板层差异。这些 差异将反过来反映出大脑区域的不同处理角色和能力。为了测试 这个假设I将使用Focus检测猕猴皮质的三个主要感觉区域 离子束/扫描电子显微镜使用高分辨率共聚焦确定详细的突触连接性 显微镜提供大规模的特定突触连接的确定，并使用中 分辨率共聚焦显微镜，以确定特定脑区的全球细胞类型分布。如果，如 我假设，不同地区之间存在着重大的数量差异，这将反映出它们的多样性 在处理角色和能力方面，这将需要对规范电路的概念进行细化。 这些定量结果对于建立现实的基于种群的皮层尖峰模型是重要的 可以再现大脑中发现的许多详细的功能特征。他们也是 重要是因为了解正常大脑的基本皮质组织是必不可少的，因为它 提供了一种标准，可以根据该标准判断哪些进程可以被更改或 在影响大脑皮层的紊乱中受损。此外，这个项目的一个重要部分是我的 作为私募股权投资的职业发展。因此，我制定了一项研究增强计划，以 增加我的研究奖学金和出版物，最终目标是获得非分数 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.