Understanding the Microcircuits in Monkey Sensory Cortices: a Connectomic Approach

了解猴子感觉皮层的微电路：连接组学方法

• 批准号: 10546501
• 负责人: Virginia Garcia-Marin
• 金额: $ 12.12万
• 依托单位: YORK COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10546501
• 关键词: 3-Dimensional; Acceleration; Affect; Amblyopia; Area; Automobile Driving; Brain; Brain region; Cell Density; Cells; Central Auditory Processing Disorder; Cerebral cortex; Characteristics; Communities; Confocal Microscopy; Data; Development; Disease; Dyslexia; Electron Microscopy; Goals; Individual; Ions; Knowledge; Label; Link; Macaca; Measures; Methods; Mission; Modeling; Monkeys; Morphology; Neurodevelopmental Disorder; Neurons; Outcome; Performance; Population; Predisposition; Presynaptic Terminals; Process; Property; Public Health; Publications; Reporting; Research; Research Support; Resolution; Role; Scanning Electron Microscopy; Schizophrenia; Scholarship; Sensory; Sensory Disorders; Structure; Surface; Synapses; System; Technology; Testing; Thalamic structure; Thinking; United States National Institutes of Health; Work; cell type; connectome; connectome data; density; design; excitatory neuron; imaging Segmentation; inhibitory neuron; inter-individual variation; large scale data; nonhuman primate; population based; reconstruction; sensory cortex; somatosensory; species difference

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.

抽象的 串行共聚焦和电子显微镜（EM）以及自动图像的发展 分割使我们能够阐明皮质回路的某些结构细节 细胞和突触水平。此信息至关重要，因为 电路在不同大脑区域及其功能的形态学特性。广泛接受的是 皮层的规范微电路是跨皮质的重复基序。一旦结构和 理解局部基序中的功能可以在所有皮质上应用。但是，最近 已显示出有主要的层流，区域和物种差异需要将其纳入 该模型的帐户。在感官区域的规范电路的另一个重要特征是 最初的丘脑皮质（TC）在皮质中驱动第4层的输入（假定是弱的）需要 大规模放大以获得观察到的尖峰速率。但是，最近的研究表明 TC弱的假设已低估了TC强度2-4倍。我假设， 尽管规范电路可能为皮质电路的功能提供一般框架，但多样 感觉大脑区域在其神经元和突触分布方面具有主要的层流差异。这些 反过来，差异将反映大脑区域的多种处理作用和能力。测试 这个假设我将使用聚焦研究猕猴皮层中的三个主要感觉区域 使用高分辨率共焦 显微镜可以大规模确定特定的突触连通性，并使用中间 分辨率共聚焦显微镜确定特定大脑区域中的全球细胞类型分布。如果， 我假设，区域之间存在重大的定量差异，这些差异将反映其多样化 处理角色和功能，这将需要对规范电路的概念进行改进。 这些定量结果对于建立基于人口的基于人口的尖峰模型很重要 可以重现大脑中发现的许多详细功能特征。他们也是 重要的是因为了解正常大脑的基本皮质组织至关重要，因为 提供可以判断它的标准，可以看到哪些过程可以更改或 影响大脑皮层的疾病受损。此外，这个项目的重要部分是我 专业发展作为PI。因此，我制定了一个研究增强计划 提高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。