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: 10294401
• 负责人: Gabe J Murphy
• 金额: $ 32.23万
• 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/10294401
• 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 (Brain); Hypersomnias; Image; Individual; 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; base; cognitive function; cortex mapping; dynamic system; excitatory neuron; experimental study; frontal lobe; imaging informatics; in vivo; motor disorder; neural circuit; neural patterning; neurotransmission; novel; relating to nervous system; 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.

摘要，项目1（全面地绘制中尺度丘脑圆圈 路由皮层输入到额叶皮层） 额叶皮层显示了动作计划，决策和短暂的神经活动的丰富模式 术语内存。在整个大脑中，皮层强烈耦合并依赖于丘脑，丘脑 代表前脑的中心枢纽。在这里，我们绘制电路涉及非感官（“高阶”） 丘脑从基底神经节，中脑，小脑和海马到额叶皮层的输入。 我们的总体假设是每个皮层下输入通过丘脑来控制额叶皮层的活性 和相关的行为。这个想法是在链接动态系统视图的建模框架中形式化的 多区域神经循环的神经功能（项目5）。该模型需要受到约束 中尺度（区域到区域）电路图通过丘脑将亚皮质与额叶皮层连接起来。但是，存在 解剖信息不足以指导体内电生理学（项目3，4）或发展 计算模型（项目5）。因此，亚皮肤皮层的细尺度中尺度图→丘脑→额叶 需要皮层电路以通过这些区域了解信号。在这个项目中，我们结合了现有的 高通量成像的管道和尖端，跨型顺序和逆行的信息 病毒追踪方法和新型记者小鼠。这些严格而全面的实验将创建 额叶皮层和非感官丘脑之间的细微尺度图（AIM 1）；发现皮质下输入到 丘脑皮质（TC）细胞的不同种群（AIM 2）；和地皮层输入到丘脑，包括 丘脑区域和单个TC细胞水平的差异和收敛（AIM 3）。处理 原始图像数据将被注册到标准化的坐标框架，并在 向社区访问的方式。