Impact of subcortical inputs on frontal cortex via thalamus

总结，项目3(皮质下输入通过丘脑对额叶皮质的影响) 这个项目的目标是阐明皮质下输入通过非脑电活动对额叶皮质的功能影响。 感觉(高级)丘脑。额叶皮质的每一部分都接受来自多个丘脑核团的输入， 每一个脑区依次接受来自不同皮质下脑区的输入。我们最近的工作已经确立了 明确不同的丘脑输入如何与特定群体的锥体细胞和中间神经元接触 在额叶皮质。然而，我们仍然缺乏对皮质下输入如何组织的基本了解 在丘脑，包括它们是如何在丘脑核团和单一丘脑皮质(TC)水平上传递的 细胞。在这里，我们测试了这样的假设，即每个皮质下的输入要么兴奋，要么抑制已定义的TC子集 参与额叶皮质特定网络的细胞。在目标1中，我们使用电生理学来研究 特定皮质下输入对完整大脑中丘脑和皮质的组织和影响。这部作品 利用新的高密度神经像素2.4探头，可以对整个丘脑的TC细胞活动进行密集采样 原子核。这些实验将定义丘脑的会聚和发散规则，并确定如何 皮质下信号传播到额叶皮质。在目标2中，我们使用脑片电生理来确定 丘脑中已识别的TC细胞的皮质下连接的特性。我们结合了Patch-Seq分析 评估每个记录的神经元的基因表达，将皮质下输入的处理与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，提供了对 与丘脑的皮质下连接。在目标3中，我们使用切片中的电压成像来检查有多具体 皮质下-丘脑通路参与额叶皮质的不同网络，主要集中在前额内侧 大脑皮层和运动皮质。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工具 然后参与额叶皮质中的特定网络。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，再次允许亚群被确定。在一起，我们的 实验将建立从皮质下输入到更高阶的连接的组织和性质 丘脑，然后是额叶皮质。它们将为我们在项目中的行为研究奠定坚实的基础 4，并对项目5中开发的神经计算的多区域模型进行约束。

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.