P4: Multiregion interactions

项目概要/摘要：项目4，多区域互动 到目前为止，我们的U19项目主要集中在单个大脑区域如何支持工作记忆 and decision-making决策.虽然这项工作已经确定了一个庞大的区域网络， 我们现在需要了解这些区域如何相互作用。哪些信息 什么时候在哪个地区之间发送这种交互如何取决于任务需求？此项目的 我们的目标是通过结合尖端的记录方法，在细胞类型， 具体的扰动，新的计算方法和一组决策任务。 我们建议收集两个数据集的多区域，大规模，细胞分辨率的记录（目标1）。 首先，我们将使用下一代Neuropixels从一个大型区域网络中同时记录 NXT技术。在第二个实验中，我们将用我们的显微镜同时从三个区域成像， 通过核心4，神经解剖学获得细胞类型特异性信息。对于这两个数据集，我们将应用新的 我们已经开发出的方法来估计跨区域的时间依赖性信息流。 除了这个广泛的大规模调查，我们还将进行两个更有针对性的实验。在 基底神经节，我们将解决的难题是如何干扰的神经活动，是不是选择性的， 然而，通过将细胞类型特异性扰动与下游记录相结合， (Aim 2）。我们也将讨论小脑在认知中的角色这一广泛而最近突出的问题 (Van Overwalle 2020;瓦格纳2020; Stoodley 2021）。通过操纵小脑群体，同时记录 丘脑和皮层，我们将测试的假设，类比小脑的作用，在完善和 稳定运动轨迹，这个区域也用于改善和稳定额叶的神经轨迹。 目标3（Aim 3）。 总之，我们希望这些实验和计算方法将提供 为多区域描述决策如何形成奠定了基础，这将提供重要的 我们在项目5中的多区域机械模型的约束。这项工作将大大促进三个 脑倡议的优先领域：大脑在行动，证明因果关系，并确定基本的 原则

Project Summary/Abstract: Project 4, Multi-Region Interactions So far, our U19 program has largely focused on how individual brain regions support working memory and decision-making. While this work has identified a large network of regions that contribute to decision-making, we now need to understand how these regions interact with each other. What information is sent between which regions, and when? How does such interaction depend on task demands? This project’s goal is to address these gaps by combining cutting-edge recording methods, recordings during cell-type- specific perturbations, new computational methods, and a panel of decision-making tasks. We propose to collect two datasets of multi-region, large-scale, cellular-resolution recordings (Aim 1). In the first, we will record simultaneously from a large network of regions, using next-generation Neuropixels NXT technology. In the second, we will image simultaneously from three regions with our mesoscope while obtaining cell-type-specific information through Core 4, Neuroanatomy. For both datasets, we will apply new methods that we have developed to estimate time-dependent information flow across regions. In addition to this broad, large-scale survey, we will perform two more targeted experiments. In the basal ganglia, we will address the puzzle of how perturbation of neural activity that is not choice selective can nevertheless lead to choice biases, by combining cell-type-specific perturbations with downstream recordings (Aim 2). We will also address the broad and recently prominent question of the cerebellum’s role in cognition (Van Overwalle 2020; Wagner 2020; Stoodley 2021). By manipulating cerebellar populations while recording in thalamus and cortex, we will test the hypothesis that, by analogy to the cerebellum’s role in refining and stabilizing motor trajectories, this region also serves to refine and stabilize neural trajectories in frontal association areas (Aim 3). Taken together, we expect that these experimental and computational approaches will provide the foundation for a multi-region description of how decisions are formed, which will provide important constraints for our multi-region mechanistic model in Project 5. This work will substantially advance three priority areas of the BRAIN Initiative: the brain in action, demonstrating causality, and identifying fundamental principles.