Bridging Function, Connectivity, and Transcriptomics of Mouse Cortical Neurons

小鼠皮质神经元的桥接功能、连接性和转录组学

• 批准号: 10688081
• 负责人: ANTON ARKHIPOV
• 金额: $ 283.39万
• 依托单位: ALLEN INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688081
• 关键词: Anatomy; Animals; Architecture; Area; Arousal; Atlases; Brain; Calcium; Cells; Characteristics; Code; Communities; Complement; Computer software; Data; Data Analyses; Data Set; Disease; Electron Microscopy; Electrophysiology (science); Evolution; Fluorescent in Situ Hybridization; Future; Gene Expression; Gene Expression Profile; Grain; Image; In Situ Hybridization; Individual; Infrastructure; Knowledge; Learning; Link; Location; Locomotion; Maps; Measures; Methods; Mission; Modality; Molecular; Monitor; Morphology; Motion; Motor Activity; Movement; Mus; Nature; Neurons; Neurosciences; Noise; Pathology; Pathway interactions; Pattern; Process; Property; Research; Resources; Role; Stimulus; Stream; Structure; Subcellular Anatomy; Taxonomy; Time; Tissue imaging; Tissues; Visual; Visual Cortex; area V1; area striata; awake; brain cell; cell type; connectome data; data sharing; electrical property; excitatory neuron; experimental study; in vivo; in vivo calcium imaging; in vivo imaging; inhibitory neuron; lens; microscopic imaging; movie; neural; neuroimaging; online resource; patch sequencing; preference; reconstruction; response; segregation; tool; transcriptomics; visual information; visual processing; visual stimulus

Bridging Function, Connectivity, and Transcriptomics of Mouse Cortical Neurons The versatile and powerful functional properties of the brain are reflected in the neuronal activity patterns and computations, and their evolution over time due to learning, homeostatic plasticity, and other processes. The composition of brain circuits out of a large number of cell types, which may be defined by the characteristic patterns of gene expression, and the intricate connectivity of these circuits are expected to be intimately related to their functional properties. However, the exact nature of these relationships is far from clear. The concept of a cell type itself, especially when considered at a fine-grained level, with a hundred or more cell types in any given brain area, is under active research in the community. A central question is whether and how transcriptomically-defined cell types provide specific underpinnings for broader circuit properties, such as those expressed in anatomy – defined by neuron’s location, morphology, connectivity – or in the functional types of neuronal activity in vivo. The proposed project will address this question by investigating the links between molecular and anatomical cell types to circuits and function in the mouse primary visual cortex (V1). We will connect the types of functional visual responses in vivo with transcriptomic types via multiplexed fluorescence in-situ hybridization (mFISH). Calcium imaging of neural activity will be carried out across the full cortical depth in V1, co-registered with mFISH imaging of that tissue, and the transcriptomic types of the neurons will be determined, establishing links between each neuron’s function and its type. In parallel, we will use a unique functional connectomics dataset already obtained at the Allen Institute, in which Electron Microscopy (EM) images are co-registered with in vivo imaging data from V1. These data will permit us to map the functional properties of each neuron to its morphological type and connectivity characteristics, resolved in the EM volume. The morphological type will, in turn, allow us to compare this dataset with the transcriptomic types, using our earlier PatchSeq dataset, where triple-modality data of morphology, intrinsic electrophysiology, and transcriptomics was obtained for individual neurons. These data and analyses will be freely shared with the scientific community. We will provide a web-based resource through the Allen Institute Cell Type Cards portal, linking across transcriptomic, morphological, connectivity, and functional types in these datasets. Thus, this project will uncover the relations between transcriptomic types, cortical circuit structure, and its function, while providing a major resource for a broad spectrum of future studies in this area.

小鼠皮质神经元的桥接功能、连接性和转录组学 大脑的多功能和强大的功能特性反映在神经活动模式和 计算，以及由于学习、稳态可塑性和其他过程而随时间的演变。 由大量细胞类型组成的脑回路的组成，可以通过特征来定义 基因表达模式以及这些电路的复杂连接预计将密切相关 与其功能特性有关。 然而，这些关系的确切性质尚不清楚，尤其是细胞类型本身的概念。 当在细粒度的水平上考虑时，在任何给定的大脑区域有一百种或更多的细胞类型， 社区中积极的研究是转录组学是否以及如何定义细胞类型。 为更广泛的电路特性提供具体的基础，例如解剖学中表达的特性 - 定义为 神经元的位置、形态、连接性——或体内神经元活动的功能类型。 拟议的项目将通过研究分子和解剖学之间的联系来解决这个问题 小鼠初级视觉皮层 (V1) 中的细胞类型与电路和功能之间的关系我们将连接以下类型。 通过多重荧光原位杂交实现体内转录组类型的功能性视觉反应 (mFISH) 神经活动钙成像将在 V1 的整个皮质深度进行，共同注册。 通过该组织的 mFISH 成像，将确定神经元的转录组类型，建立 每个神经元的功能及其类型之间的联系。 与此同时，我们将使用艾伦研究所已获得的独特功能连接组学数据集， 电子显微镜 (EM) 图像与 V1 的体内成像数据共同配准。 允许我们将每个神经元的功能特性映射到其形态类型和连接性 特征，在 EM 体积中解析，反过来，形态类型将允许我们对此进行比较。 具有转录组类型的数据集，使用我们之前的 PatchSeq 数据集，其中三模态数据 获得了单个神经元的形态学、内在电生理学和转录组学。 这些数据和分析将与科学界自由共享，我们将提供基于网络的信息。 通过艾伦研究所细胞类型卡门户获取资源，跨转录组、形态学、 这些数据集中的连通性和功能类型。 因此，该项目将揭示转录组类型、皮质回路结构及其功能之间的关系。 功能，同时为该领域未来的广泛研究提供主要资源。