Functional connectomics of the neocortical microcircuit

新皮质微电路的功能连接组学

• 批准号: 8740484
• 负责人: RAFAEL YUSTE
• 金额: $ 80万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8740484
• 关键词: Affect; Appearance; Area; Award; Calcium; Cells; Cerebral cortex; Data; Disease; Epilepsy; Functional disorder; Head; Image; Individual; Information Distribution; Label; Logic; Maps; Mental disorders; Methods; Modeling; Mus; Neurons; Optical Methods; Pattern; Population; Preparation; Psyche structure; Resolution; Rest; Running; Sampling; Schizophrenia; Sensory; Site; Structure; Synapses; Techniques; Testing; Time; Transgenic Organisms; Work; awake; base; cognitive function; in vivo; neocortical; neural circuit; novel; research study; theories; two-photon

DESCRIPTION (provided by applicant): Functional Connectomics of the Neocortical Microcircuit The cortex constitutes the primary site of higher cognitive functions and mental disease. No unified theory of how the cortex works exists yet, due to our basic ignorance about its microcircuits (i.e. the detailed connectivity patterns of any cortical area), and also because it is likely that its function is based on an emergent level, determined by the states of activity of large neuronal ensembles. Two-photon calcium imaging and photo-activation techniques enable us to simultaneous record and optically manipulate the activity of larger neuronal populations, while maintaining single cell resolution. Using such techniques we have encountered signs of what could be a highly distributed and essentially random cortical microcircuit. Based on these results, we propose the idea that the cortex is a random circuit, meaning that each synaptic connection is chosen by chance, independently from others. These circuits, mathematically analogous to completely connected ones, would maximize the distribution of information and enable the appearance of emergent functional states. This model runs contrary to the traditional view of the cortex, one that arose from sampling individual neurons, as a very specific machine where the connectivity and function of each neuron is precisely determined. Using this award, I want to test the hypothesis that the cortex is a random network, applying novel two-photon methods in a large-scale and systematic study of the mouse cortical microcircuit. I propose a three-pronged approach: 1- Image the activity of an entire cortical module in a mouse, to detect all spikes from all cells. 2- Perform a “Circuit Cracker” analysis to obtain the blueprint of connectivity of the module. 3- Optically manipulate the population activity to test whether it behaves as a random circuit. Experiments will be done in mouse cortex in vivo, with awake, head-restrained preparations, under sensory stimulation and rest. Transgenic strains will be used to selectively label identified subpopulations of cells, and several cortical areas will be examined to explore common modular features. The proposed work will provide, for the first time, a complete description of the activity of any neural circuit and the blueprint of the cortical circuit and will pioneer “Functional Connectomics”, i.e., deciphering the connectivity of the circuit from its functional correlations. If the data confirm that the microcircuit is indeed random, our results could also usher in a novel model for cortical function, one based on the existence of emergent functional states. This model could replace the current paradigm, and enable a more efficient understanding of the pathophysiology of cortical diseases, such as epilepsy and schizophrenia.

描述（应用程序提供）：新皮质微电路的功能连接 皮质构成了较高的认知功能和精神疾病的主要部位。没有统一 由于我们对其微电路的基本无知（即 任何皮质区域的详细连接模式），也是因为它的功能可能基于 在紧急水平上，由大型神经元合奏的活动状态决定。 两光子钙成像和光激活技术使我们能够同时记录和 光学地操纵较大的神经元群体的活性，同时保持单细胞分辨率。 使用这样的技术，我们遇到了可能是高度分布的迹象 随机皮质微电路。基于这些结果，我们提出了这样的想法，即皮层是随机的 电路，这意味着每个综合连接都是偶然选择的，独立于其他合成连接。 电路，在数学上类似于完全连接的电路，将最大化 信息并实现出现新兴功能状态。该模型与 皮质的传统视图，它是由单个神经元进行采样的，是非常具体的 精确确定每个神经元的连通性和功能的机器。 使用该奖项，我想检验以下假设：皮质是一个随机网络，应用小说 小鼠皮质微电路的大规模和系统研究中的两光子方法。 我提出了一种三管齐下的方法： 1-图像小鼠中整个皮质模块的活性，以检测所有细胞的所有峰值。 2-执行“电路饼干”分析以获得模块连通性的蓝图。 3-光学操纵种群活动以测试其是否表现为随机电路。 实验将在体内鼠标皮层中进行，并在醒着，头部张力的准备工作下进行 感觉模拟和休息。转基因菌株将用于选择性标记鉴定的亚群 细胞和几个皮质区域将进行检查以探索常见的模块化特征。 拟议的工作将首次提供任何中性活动的完整描述 电路和皮层电路的蓝图，并将开拓“功能连接”，即 从其功能相关性中解释电路的连通性。如果数据确认 微电路确实是随机的，我们的结果也可能引入一个新型的皮质功能模型，一个 基于新兴功能状态的存在。该模型可以替换当前范式， 并使对皮质疾病的病理生理学有更有效的理解，例如癫痫 和精神分裂症。