Produce the cell-type-specific thalamocortical projectome

产生细胞类型特异性丘脑皮质投射组

• 批准号: 10546513
• 负责人: Bosiljka Tasic
• 金额: $ 83.38万
• 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: 2022-01-15 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10546513
• 关键词: Address; Ally; Anatomy; Anterior; Area; Atlases; Axon; BRAIN initiative; Behavior; Brain; Brain region; Categories; Cells; Censuses; Cerebellum; Classification; Color; Communities; Complex; Coupled; Data; Data Science Core; Data Set; Event; Fluorescent in Situ Hybridization; Foundations; Gene Expression; Gene Expression Profiling; Genetic; Genetic Markers; Goals; Hippocampus; Individual; Knowledge; Label; Lateral; Link; Location; Mammals; Maps; Measures; Medial; Methodology; Methods; Midbrain structure; Molecular; Morphology; Motor Cortex; Movement; Multiregional Analyses; Mus; Neocortex; Neurons; Output; Pattern; Physiology; Prefrontal Cortex; Prosencephalon; RNA; Resolution; Science; Sensory; Shapes; Short-Term Memory; Signal Transduction; Spatial Distribution; Taxonomy; Thalamic Nuclei; Thalamic structure; Work; cell type; excitatory neuron; flexibility; frontal lobe; genetic approach; genetic selection; multimodal data; multimodality; neocortical; neural circuit; neural patterning; reconstruction; single-cell RNA sequencing; tool; transcriptomics; transmission process

Summary, Project 2 (Produce the cell type-specific thalamocortical projectome) Frontal cortex displays rich patterns of neural activity, which can be decomposed into 'activity modes' corresponding to specific aspects of behavior (see Overall), such as the persistent activity correlated with short- term memory, and rapidly cycling activity causing voluntary movements. Frontal cortex is strongly coupled to the thalamus, the central hub of the forebrain. Subcortical information flows through the thalamus to the cortex. Most of thalamus is non-sensory (‘higher-order’), with input from cerebellum, multiple parts of the midbrain, and hippocampus, and outputs to most cortical areas (a detailed map of inputs is part of Project 1). This project aims to uncover the thalamocortical (TC) cell types. These are excitatory neurons that receive input from subcortical areas outside of the thalamus and project to the neocortex. Understanding TC types is critical because distinct TC types likely correspond to specialized thalamocortical channels for transmission of information from sub- cortex to cortex. We currently lack even a rudimentary conceptual framework for the function of non-primary- sensory thalamus, in part because our knowledge of subcortex-thalamus-cortex circuits is at a nascent stage. A limited set of morphological reconstructions have shown that the TC neurons are diverse across and within thalamic nuclei defined by cytoarchitecture. Our preliminary data suggest that different control signals arise in different subcortical areas, with distinct effects on cortical activity modes. The input-output rules at the level of individual thalamocortical (TC) cells constrain the possible control strategies. Are subcortical control signals routed through independent TC types or even different thalamic nuclei (‘labeled lines’)? Or do multiple subcortical inputs converge at the level of TC cells, with individual TC types transmitting a mixture of control signals? To help address these questions we will establish a census of TC types across the higher-order thalamus, including neurons projecting to anterior lateral motor cortex (ALM) and medial prefrontal cortex (mPFC). We will use new methods that combine morphological reconstructions of entire TC neurons with transcriptomics for the same cells. We refer to cells defined in this manner as morpho-transcriptomic (m-t) TC types. We will further densely map cell types defined by transcriptomics, so-called t-types, across the entire thalamus. By linking morphology, transcriptomics and location at the single neuron level, these data will provide the foundation for genetic access of specific TC types (strategies for genetic access will be developed in the Molecular Science Core). Together, this information will create knowledge and tools for cell type-specific analysis of multi-regional circuits (Projects 3, 4) with thalamus in the middle.

摘要，项目2（生产细胞类型特异性的丘脑皮层projectome） 额叶皮层显示丰富的神经活动模式，可以分解为“活动模式” 对应于行为的特定方面（请参阅总体），例如持续活动与短期相关 术语记忆和迅速骑自行车活动导致自愿运动。额叶皮质与 丘脑，前脑的中心枢纽。皮质下信息通过丘脑流向皮层。最多 丘脑的含量是非感官（“高阶”），来自小脑的输入，中脑的多个部分，并且 海马和向大多数皮质区域的输出（输入的详细地图是项目1的一部分）。这个项目的目标 发现丘脑皮质（TC）细胞类型。这些是兴奋性神经元，从皮层下接收输入 丘脑之外的区域并投射到新皮层。了解TC类型至关重要，因为独特 TC类型可能对应于专门的丘脑皮质通道，以传输来自子的信息 皮质到皮质。目前，我们甚至缺乏针对非主要概念的基本概念框架 感觉丘脑，部分原因是我们对亚皮层 - thalamus-cortex电路的了解是在一个新生的阶段。 一组有限的形态重建表明，TC神经元在各个方面和内部是潜水员 丘脑核由细胞结构定义。我们的初步数据表明，不同的控制信号在 皮质下不同的区域，对皮质活性模式有明显的影响。输入输出规则在 单个丘脑皮层（TC）细胞控制可能的控制策略。是皮层控制信号 通过独立的TC类型或什至不同的丘脑核（“标记的线”）进行路由？或做多层皮层 输入在TC细胞的水平上收敛，单个TC类型会传递控制信号的混合物？ 为了帮助解决这些问题，我们将在高阶丘脑中建立TC类型的普查， 包括投射到前侧运动皮层（ALM）和培养基前额叶皮层（MPFC）的神经元。我们将 使用将整个TC神经元与转录组学结合形态重建的新方法 相同的细胞。我们将以这种方式定义的细胞称为形态转录组（M-T）TC类型。我们将进一步 在整个丘脑中，由转录组学，所谓的T型定义的无映射细胞类型。通过链接 形态学，转录组学和位置在单个神经元级别，这些数据将为 特定TC类型的遗传获取（分子科学将开发遗传获取策略 核）。这些信息将共同创建知识和工具，用于多区域的特定于单元类型的分析 电路（项目3，4）与丘脑在中间。