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.

总结，项目2(制作特定细胞类型的丘脑皮质项目组) 额叶皮质显示出丰富的神经活动模式，这些模式可以分解为“活动模式”。 对应于行为的特定方面(参见整体)，例如与短的相关的持续活动- 术语记忆，以及导致自主运动的快速自行车运动。额叶皮质强烈地耦合到 丘脑，前脑的中心中枢。皮质下信息通过丘脑流向大脑皮层。多数 丘脑是无感觉的(更高级的)，输入来自小脑、中脑的多个部分，以及 海马区，并输出到大多数皮质区域(输入的详细地图是项目1的一部分)。这个项目的目的是 以揭示丘脑皮质(TC)细胞类型。这些兴奋性神经元接受皮质下的输入。 丘脑以外的区域并投射到新皮质。理解TC类型至关重要，因为不同于 TC类型可能对应于专门的丘脑皮质通道，用于从亚脑 皮质到皮质。我们目前甚至缺乏一个基本的概念框架来发挥非主要的- 感觉丘脑，部分是因为我们对皮质下-丘脑-皮质回路的了解还处于初级阶段。 一组有限的形态重建表明，TC神经元在不同的区域和内部是不同的。 丘脑核团由细胞结构定义。我们的初步数据表明，不同的控制信号在 不同的皮质下区域，对皮质活动模式有不同的影响。层面上的投入产出规则 单个丘脑皮质(TC)细胞限制了可能的控制策略。是皮质下控制信号 通过独立的TC类型或者甚至不同的丘脑核团(“标记线”)？或做多个皮质下 输入在TC信元级别汇聚，各个TC类型传输混合的控制信号？ 为了帮助解决这些问题，我们将对高阶丘脑的TC类型进行普查， 包括投射到前外侧运动皮质(ALM)和内侧前额叶皮质(MPFC)的神经元。我们会 使用新的方法，将整个TC神经元的形态重建与转录切割相结合 同样的细胞。我们将以这种方式定义的细胞称为形态转录型(m-t)TC型。我们将进一步 在整个丘脑中密集地映射由转录切割定义的细胞类型，即所谓的t型。通过链接 在单个神经元水平上的形态、转录和定位，这些数据将为 特定TC类型的遗传获取(遗传获取策略将在分子科学中制定 核心)。这些信息将共同创建用于多区域特定细胞类型分析的知识和工具 丘脑位于中间的环路(方案3、4)。