Impact of subcortical inputs on frontal cortex via thalamus

皮层下输入通过丘脑对额叶皮层的影响

• 批准号: 10294403
• 负责人: Adam G Carter
• 金额: $ 51.91万
• 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/10294403
• 关键词: Abbreviations; Anatomy; Behavior; Behavioral; Brain; Brain region; Cell Nucleus; Cells; Cognitive; Color; Electrophysiology (science); Foundations; Gene Expression; Globus Pallidus; Goals; Image; Individual; Interneurons; Knowledge; Link; Medial; Modeling; Molecular; Motor Cortex; Neurons; Pathway interactions; Pharmacology; Physiological; Physiology; Population; Prefrontal Cortex; Property; Pyramidal Cells; Rewards; Route; Sampling; Science; Signal Transduction; Site; Slice; Substantia nigra structure; Synapses; Testing; Thalamic Nuclei; Thalamic structure; Virus; Work; base; behavior influence; behavioral study; cell type; density; experimental study; frontal lobe; genetic approach; genetic signature; in vivo; neural circuit; neural model; optogenetics; patch sequencing; relating to nervous system; response; sensory cortex; tool; transcriptomics; voltage

Summary, Project 3 (Impact of subcortical inputs on frontal cortex via thalamus) The goal of this project is to elucidate the functional influence of subcortical inputs on the frontal cortex via non- sensory ('higher-order') thalamus. Each part of the frontal cortex receives inputs from multiple thalamic nuclei, each of which in turn receives inputs from diverse subcortical brain regions. Our recent work has established clear motifs for how different thalamic inputs can engage specific populations of pyramidal cells and interneurons in the frontal cortex. However, we still lack even a basic understanding of how subcortical inputs are organized in the thalamus, including how they are routed at the level of thalamic nuclei and single thalamocortical (TC) cells. Here we test the hypothesis that each subcortical input either excites or inhibits a defined subset of TC cells to engage specific networks in the frontal cortex. In Aim 1, we use electrophysiology to study the organization and influence of specific subcortical inputs on the thalamus and cortex in the intact brain. This work leverages new, high-density Neuropixels 2.4 probes that allow dense sampling of TC cell activity across thalamic nuclei. These experiments will define convergence and divergence rules in the thalamus and determine how subcortical signals propagate to frontal cortex. In Aim 2, we use brain slice electrophysiology to determine the properties of subcortical connections onto identified TC cells in the thalamus. We incorporate patch-Seq analysis to assess gene expression of each recorded neuron, linking processing of subcortical inputs with TC cell type. This work builds on Projects 1 and 2 and the Molecular Science Core, providing a foundational analysis of subcortical connections to the thalamus. In Aim 3, we then use voltage imaging in slices to examine how specific subcortical-thalamic pathways engage distinct networks across the frontal cortex, focusing on medial prefrontal cortex and motor cortex. Here we use anterograde viruses to conditionally express optogenetic tools in TC cells that then engage specific networks in the frontal cortex. We also employ mFISH to assess the genetic signatures of imaged excitatory and inhibitory cells, again allowing for sub-populations to be determined. Together, our experiments will establish the organization and properties of connections from subcortical inputs to higher-order thalamus and in turn the frontal cortex. They will serve as a strong foundation for our behavioral studies in Project 4, and constrain multi-regional models of neural computation developed in Project 5.

总结，项目3（皮层下输入通过丘脑对额叶皮层的影响） 本研究的目的是阐明皮层下输入通过非- 感觉（“高级”）丘脑。额叶皮层的每一部分都接收来自多个丘脑核团的输入， 每一个又从不同的皮层下大脑区域接收输入。我们最近的工作已经确定 明确了不同的丘脑输入如何参与锥体细胞和中间神经元的特定群体 大脑额叶皮层然而，我们仍然缺乏对皮层下输入是如何组织的基本理解， 包括它们如何在丘脑核团和单个丘脑皮质（TC）水平上路由 细胞在这里，我们测试的假设，每个皮层下的输入要么兴奋或抑制一个定义的子集TC 这些细胞与额叶皮层中的特定网络连接。在目标1中，我们使用电生理学来研究 在完整的大脑中，特定的皮层下输入对丘脑和皮层的组织和影响。这项工作 利用新的高密度Neuropixels 2.4探针，可对丘脑TC细胞活动进行密集采样 原子核。这些实验将定义丘脑中的会聚和发散规则，并确定 皮层下信号传播到额叶皮层。在目标2中，我们使用脑切片电生理学来确定 皮质下连接到丘脑中已识别的TC细胞的特性。我们将patch-Seq分析 评估每个记录的神经元的基因表达，将皮层下输入的处理与TC细胞类型联系起来。 这项工作建立在项目1和2以及分子科学核心的基础上，提供了以下方面的基础分析： 皮层下与丘脑的联系在目标3中，我们然后使用切片中的电压成像来检查 皮质下-丘脑通路与横跨额叶皮质的不同网络相联系，集中在内侧前额叶 皮质和运动皮质。在这里，我们使用顺行病毒在TC细胞中有条件地表达光遗传学工具 然后激活额叶皮层的特定网络。我们还使用mFISH来评估基因签名 成像的兴奋性和抑制性细胞，再次允许确定亚群。我们一起， 实验将建立从皮层下输入到高阶输入的连接的组织和性质。 丘脑和额叶皮层。它们将作为我们在项目中进行行为研究的坚实基础 4，约束多区域模型的神经计算项目5中开发的。