Integrated functional and structural analysis of an entire column in mouse primary visual cortex

项目摘要 视觉皮层中的神经元形成了复杂的连接结构和拓扑排列。的 已知神经元的结构和形态组织限制其功能特性。到 了解这些限制，有必要产生大规模的解剖和功能测量 的大脑。电子显微镜（EM）和荧光显微镜的持续努力有望大规模地 加快生成此类数据的速度。为了发现结构和功能之间的关系， 一种方法是在大脑中使用具有结构和功能组件的计算模型。 卷积神经网络（CNN），以及更广泛的机器学习（ML），已经显示出越来越多的 在模拟大脑功能特性方面的前景。然而，这些基于CNN的模型通常不是 由大脑中神经元的真实的结构引导。在这份提案中，我们试图分享和分析 迄今为止从小鼠初级视觉皮层（V1）的整个列收集的最大钙成像数据集。 我们建议将此数据集与一个单独的公开可用的电子显微镜（EM）数据集整合， 使用一种新的拓扑合理的基于CNN的神经元模型在小鼠V1中测量1 mm 3体积。我们将使用 这个新的模型来理解结构组织如何提供功能。我们的方法是 拓扑建模应用于神经网络计算的研究。钙成像数据集包括 体积2光子和3光子成像。这些数据包含了来自 初级视皮层800 μ m × 800 μ m × ~ 800 μ m区域内的神经元，跨越视觉各层 从软陶到白色物质。我们建议使用该数据集系统地表征生理 在小鼠V1中的整个列中的空间选择性和运动选择性神经元的特性。我们将 确定空间选择性神经元中ON和OFF子场的组织和大小是否以及如何 显示视觉层之间的差异。然后我们将测试的假设，空间选择性和运动- 选择性神经元在V1内形成不同的网络。我们建议将这两个网络合并到 神经元的卷积神经网络模型，以测试该模型是否导致更高的预测准确性 以及更好地估计神经模式选择性。最后，我们提出了表征的分支图案， 使用来自小鼠视觉皮层中1 mm 3体积的EM重建的小鼠V1。然后我们将整合 这些图案与基于CNN的神经元模型，以准确预测钙成像反应。我们将 使用此设置来测试在模型中引入分支基序是否会导致更准确的预测 和更好的神经模式选择性的估计。我们的建议提供了一个系统的方法， 整合结构和功能数据集，以了解结构如何在视觉皮层中提供功能。

PROJECT SUMMARY Neurons in the visual cortex form an intricate connectivity structure and topographic arrangement. The structural and morphological organization of the neurons is known to constrain its functional properties. To understand these constraints, it is necessary to generate large-scale anatomical and functional measurements of the brain. Ongoing efforts in electron microscopy (EM) and fluorescent microscopy promise to massively accelerate the speed of generating such data. To discover the relationship between structure and function, one approach is to use models of computation in the brain that have both structural and functional components. Convolutional neural networks (CNNs), and more broadly machine learning (ML), have shown an increasing promise in modeling the functional properties of the brain. However, these CNN-based models are often not guided by the real structure of the neurons in the brain. In this proposal, we seek to share and analyze the largest calcium imaging dataset collected to date from an entire column in mouse primary visual cortex (V1). We propose to integrate this dataset with a separate publicly available electron microscopy (EM) dataset of 1mm3 volume in mouse V1 using a novel topologically-plausible CNN-based model of neurons. We will use this new model to understand how the structural organization affords function. Our approach is to bring topological modeling to the study of the computation in neural networks. The calcium imaging dataset includes volumetric 2-photon and 3-photon imaging in four mice. The data contains recordings of visual responses from neurons within an 800um × 800um × ~800um region of the primary visual cortex, spanning all visual layers from pia to white matter. We propose to use this dataset to systematically characterize the physiological properties of spatially-selective and motion-selective neurons in an entire column in mouse V1. We will determine whether and how the organization and size of ON and OFF subfields in spatially-selective neurons reveal differences across visual layers. We will then test the hypothesis that the spatially-selective and motion- selective neurons form distinct networks within V1. We propose to incorporate these two networks into convolutional neural network model of neurons to test whether this model results in higher predictive accuracy and better estimation of neural pattern selectivity. Finally, we propose to characterize the branching motifs in mouse V1 using the EM reconstructions from 1mm3 volume in mouse visual cortex. We will then integrate these motifs with the CNN-based models of neurons to accurately predict calcium imaging responses. We will use this setup to test whether incorporating the branching motifs in a model result in more accurate prediction of neural activity and better estimation of neural pattern selectivity. Our proposal offers a systematic approach to integrate structural and functional datasets to understand how structure affords function in the visual cortex.