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、连接和转录 大脑的多功能性和强大的功能特性反映在神经元的活动模式和 计算，以及它们由于学习、稳态可塑性和其他过程而随时间的演变。这个 由大量细胞类型组成的大脑回路，这可以由特征来定义 基因表达的模式，以及这些回路的复杂连接预计将密切相关 与它们的功能特性有关。 然而，这些关系的确切性质还远不清楚。细胞类型本身的概念，尤其是 当考虑到细粒度水平时，在任何给定的大脑区域中有100种或更多类型的细胞， 在社区中积极开展研究。一个中心问题是，是否以及如何在转录水平上定义细胞类型 为更广泛的电路特性提供特定的基础，例如由 神经元的位置、形态、连通性--或在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。 小鼠初级视皮层(V1)的细胞类型到回路和功能。我们将连接以下类型 多重荧光原位杂交法检测转录型在体视功能反应 (MFISH)。神经活动的钙成像将在V1的全皮质深度进行，共同注册 通过对该组织的mFISH成像，将确定神经元的转录类型，建立 每个神经元的功能和它的类型之间的联系。 同时，我们将使用艾伦研究所已经获得的独特的功能连接学数据集 这些电子显微镜(EM)图像与来自V1的活体成像数据共同配准。这些数据将 允许我们将每个神经元的功能属性映射到其形态类型和连接性 特征，在EM卷中解析。形态类型反过来将允许我们比较这一点 具有转录类型的数据集，使用我们之前的PatchSeq数据集，其中 获得了单个神经元的形态、内在电生理学和转录剪切学。 这些数据和分析将免费与科学界共享。我们将提供基于Web的 通过艾伦研究所细胞类型卡门户网站，链接转录、形态、 连接性和这些数据集中的函数类型。 因此，这个项目将揭示转录类型、大脑皮层回路结构和其 功能，同时为这一领域的广泛未来研究提供主要资源。