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（产生细胞类型特异性丘脑皮质投影组） 额叶皮层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” 与行为的特定方面相对应（参见总体），例如与短- 术语记忆，以及引起随意运动的快速循环活动。额叶皮层与大脑皮层 丘脑，前脑的中枢。皮层下的信息通过丘脑流向皮层。最 丘脑是非感觉（“高阶”），输入来自小脑，中脑的多个部分， 海马，并输出到大多数皮层区域（输入的详细地图是项目1的一部分）。该项目旨在 以揭示丘脑皮质（TC）细胞类型。这些是兴奋性神经元， 丘脑外的区域并投射到新皮层。了解TC类型至关重要，因为 TC类型可能对应于专门的丘脑皮层通道，用于从下丘脑传递信息。 皮层到皮层我们目前甚至缺乏一个基本的概念框架，以发挥非主要的作用， 感觉丘脑，部分原因是我们对皮层下-丘脑-皮层回路的认识还处于初级阶段。 一组有限的形态学重建表明，TC神经元是不同的跨越和内部 由细胞结构确定的丘脑核。我们的初步数据表明，不同的控制信号出现在 不同的皮层下区域，对皮层活动模式有不同的影响。层次上的投入产出规则 单个的丘脑皮层（TC）细胞限制了可能的控制策略。是皮层下的控制信号 通过独立的TC类型或甚至不同的丘脑核（“标记线”）？还是多个皮层下 输入收敛在TC细胞的水平，与个别TC类型传输的控制信号的混合？ 为了帮助解决这些问题，我们将建立一个在高级丘脑TC类型的普查， 包括投射到前外侧运动皮层（ALM）和内侧前额叶皮层（mPFC）的神经元。我们将 使用新的方法，将整个TC神经元的联合收割机形态重建与转录组学相结合， 同样的细胞。我们将以这种方式定义的细胞称为形态转录组（m-t）TC类型。我们将进一步 在整个丘脑中密集地绘制由转录组学定义的细胞类型，即所谓的T型。通过链接 形态学、转录组学和单个神经元水平的定位，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）。总之，这些信息将为多区域细胞的细胞类型特异性分析创造知识和工具。 电路（项目3，4）与丘脑在中间。