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（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，可以分解为“活动模式” 对应于行为的特定方面（参见总体），例如与短期相关的持续活动 术语记忆和导致随意运动的快速循环活动与额叶皮层密切相关。 丘脑，前脑的中枢，信息通过丘脑流向皮质。 丘脑是非感觉的（“高阶”），输入来自小脑、中脑的多个部分，并且 海马体，并输出到大多数皮质区域（详细的输入图是项目 1 的一部分）。 揭示丘脑皮质 (TC) 细胞类型，这些细胞是接收皮质下输入的兴奋性神经元。 了解丘脑以外的区域和投射到新皮质的 TC 类型至关重要，因为它们是不同的。 TC 类型可能对应于专门的丘脑皮质通道，用于从子系统传输信息。 我们目前甚至缺乏非初级功能的基本概念框架。 感觉丘脑，部分原因是我们对皮层下-丘脑-皮层回路的了解还处于初级阶段。 一组有限的形态学重建表明 TC 神经元在内部和外部是多样化的 我们的初步数据表明，不同的控制信号出现在由细胞结构定义的丘脑核中。 不同的皮层下区域，对皮层活动模式具有不同的影响。 单个丘脑皮质 (TC) 细胞限制了可能的控制策略。 通过独立的 TC 类型甚至不同的丘脑核（“标记线”）或多个皮层下路由？ 输入在 TC 单元级别汇聚，各个 TC 类型传输控制信号的混合？ 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层（ALM）和内侧前额叶皮层（mPFC）的神经元。 使用将整个 TC 神经元的形态重建与转录组学相结合的新方法 我们将以此方式定义的细胞称为形态转录组 (m-t) TC 类型。 通过连接，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。 单神经元水平的形态学、转录组学和定位，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） 这些信息共同将为多区域的细胞类型特异性分析创建知识和工具。 丘脑位于中间的电路（项目 3、4）。