Comprehensively map the mesoscale thalamic circuits that route subcortical inputs to frontal cortex

全面绘制将皮层下输入路由至额叶皮层的中尺度丘脑回路

• 批准号: 10546512
• 负责人: Gabe J Murphy
• 金额: $ 30.69万
• 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/10546512
• 关键词: Anatomy; Anterolateral; Area; Axon; Basal Ganglia; Behavior; Brain; Brain region; Cell Nucleus; Cells; Cerebellum; Code; Cognition Disorders; Coma; Communities; Computer Models; Coupled; Data; Decision Making; Disease; Electrophysiology (science); Fluorescence; Globus Pallidus; Hippocampus; Hypersomnias; Image; Individual; Informatics; Label; Learning; Link; Location; Maps; Medial; Methods; Midbrain structure; Modeling; Motor Cortex; Movement; Mus; Neurons; Output; Pathway interactions; Population; Prefrontal Cortex; Process; Prosencephalon; Proteins; Rabies; Recurrence; Reporter; Rewards; Route; Sensory; Short-Term Memory; Signal Transduction; Source; Standardization; Substantia nigra structure; Testing; Thalamic Nuclei; Thalamic structure; Viral; Virus; Work; cognitive function; dynamic system; excitatory neuron; experimental study; frontal lobe; in vivo; motor disorder; neural; neural circuit; neural patterning; neurotransmission; novel; sensory cortex; signal processing

Summary, Project 1 (Comprehensively map the mesoscale thalamic circuits that route subcortical inputs to frontal cortex) Frontal cortex displays rich patterns of neural activity underlying action planning, decision-making, and short- term memory. Across the brain, the cortex is strongly coupled to, and dependent upon, the thalamus, which represents the central hub of the forebrain. Here we map circuits involving the non-sensory ('higher-order') thalamus, which routes input from basal ganglia, midbrain, cerebellum, and hippocampus to the frontal cortex. Our overarching hypothesis is each subcortical input acts through the thalamus to control activity in frontal cortex and associated behavior. This idea is formalized in a modeling framework that links a dynamical systems view of neural computation with multi-regional neural circuits (Project 5). This model needs to be constrained by mesoscale (region-to-region) circuit diagrams linking subcortex to frontal cortex via thalamus. However, existing anatomical information is insufficiently detailed to guide either in vivo electrophysiology (Projects 3, 4) or develop computational models (Project 5). Therefore, a fine-scale mesoscale map of subcortex → thalamus → frontal cortex circuits is required to understand signaling through these regions. In this project, we combine existing pipelines for high-throughput imaging and informatics with cutting-edge, transcellular anterograde and retrograde viral tracing methods and new types of reporter mice. These rigorous and comprehensive experiments will create a fine-scale map between frontal cortex and non-sensory thalamus (AIM 1); discover the subcortical inputs to different populations of thalamocortical (TC) cells (AIM 2); and map subcortical inputs to thalamus, including divergence and convergence at the level of both thalamic regions and individual TC cells (AIM 3). Processed and raw image data will be registered to a standardized coordinate framework and made readily available in an accessible manner to the community.

总结，项目1（全面绘制中尺度丘脑回路， 将皮层下输入传递到额叶皮层） 额叶皮层显示出丰富的神经活动模式，这些神经活动是行动计划、决策和短期行为的基础。 术语记忆在整个大脑中，皮质与丘脑紧密相连，并依赖于丘脑，丘脑 代表着前脑的中枢在这里，我们映射涉及非感觉（'高阶'）的电路 丘脑，其将来自基底神经节、中脑、小脑和海马体的输入路由到额叶皮质。 我们的总体假设是，每一个皮层下的输入都通过丘脑来控制额叶皮层的活动 和相关的行为。这个想法在链接动力系统视图的建模框架中得到了形式化 多区域神经回路的神经计算（项目5）。这种模式需要受到 中尺度（区域到区域）电路图，通过丘脑连接皮层下和额叶皮层。但现有 解剖信息不够详细，无法指导体内电生理学（项目3，4）或开发 计算模型（项目5）。因此，皮层下→丘脑→额叶的精细中尺度图 皮层回路是理解通过这些区域的信号传递所必需的。在这个项目中，我们将现有的联合收割机 用于高通量成像和信息学的管道，具有尖端的跨细胞顺行和逆行 病毒追踪方法和新型报告小鼠。这些严谨而全面的实验将创造 额叶皮层和非感觉丘脑（AIM 1）之间的精细比例图;发现皮层下输入， 不同群体的丘脑皮质（TC）细胞（AIM 2）;并将皮质下输入映射到丘脑，包括 在丘脑区域和单个TC细胞水平上的发散和会聚（AIM 3）。处理 并且原始图像数据将被配准到标准化坐标框架， 对社区的开放方式。