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图 将皮质下输入传递到额叶皮质) 额叶皮质显示出丰富的神经活动模式，支持行动计划、决策和短时- 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 代表了前脑的中央中枢。在这里，我们绘制了涉及非感官的回路(“高阶”)。 丘脑，它将来自基底节、中脑、小脑和海马体的信息传递到额叶皮质。 我们最重要的假设是，每个皮质下的输入都通过丘脑控制额叶皮质的活动。 以及相关联的行为。这一想法在链接动态系统视图的建模框架中形式化 多区域神经电路的神经计算(项目5)。此模型需要受以下约束 中尺度(区域到区域)电路图，通过丘脑连接皮质下和额叶皮质。然而，现有的 解剖学信息不够详细，不足以指导活体电生理学(项目3、4)或开发 计算模型(项目5)。因此，一张精细的中尺度皮层下→丘脑→额叶地图 大脑皮层电路是理解通过这些区域的信号所必需的。在这个项目中，我们结合了现有的 具有前沿、跨细胞顺行和逆行的高通量成像和信息学管道 病毒追踪方法和新型报告鼠。这些严谨而全面的实验将创造出 额叶皮质和非感觉性丘脑之间的精细地图(目标1)；发现皮质下输入 不同数量的丘脑皮质(TC)细胞(AIM 2)；并将皮质下输入映射到丘脑，包括 丘脑区和单个TC细胞水平的发散和融合(AIM 3)。已处理 原始图像数据将被记录到标准化的坐标框架中，并在 以社区可及的方式。