Causal brainwide interactions underlying internal states and decisions

摘要/摘要，项目2 即使在相同的环境中，动物也可能在不同的场合做出不同的决定，因为它的 内部状态，如参与一项任务，与外部输入强有力地相互作用，以决定行为。 这项提案的首要目标是了解内部国家如何影响决策，并确定 潜在的神经机制。该团队是国际脑实验室(IBL)的一部分，该实验室是一个老牌的 开发了标准化的鼠标决策任务和标准化方法的财团 培训、神经测量和数据分析，以及用于共享数据的有效、可扩展的基础设施。 项目2的目标是确定大脑区域和细胞类型对区域间的因果影响 在特定时间积分光遗传扰动的通信和状态依赖决策 在任务期间，同时记录神经种群和功能超声。我们会考虑 两种类型的内部状态：忙碌/不忙碌的任务绩效和由于统计而产生的左/右偏差 环境的结构，这在不同的试验块中是不同的。在目标1中，我们将研究皮质下的作用 训练有素的小鼠进行系统光遗传操作时状态依赖决策的结构 执行IBL决策任务。在目标2中，我们将检查抑制靶区和/或细胞的因果效应 使用神经像素探头和功能超声对其他区域之间的通信感兴趣的类型。 在目标3中，为了整合我们的结果，我们将建立多区域人口的动态计算模型 在我们的因果操控过程中的活动。这些模型将在一个大脑中解释操作的影响。 区域对其他区域的行为和活动及其对内部状态的依赖。结果将会有所帮助 解释我们的实验，并通过建议要记录和操作的其他区域组合来改进它们。 总之，这些实验将结合尖端的实验和计算方法来表征 全脑区域的因果相互作用及其对内部状态的依赖。

Summary/Abstract, Project 2 Even in the same environment, an animal may make different decisions on different occasions, because its internal state, such as engagement in a task, interacts powerfully with external inputs to determine behavior. This proposal’s overarching goal is to understand how internal states influence decisions and to identify the underlying neural mechanisms. The team is part of the International Brain Laboratory (IBL), an established consortium that has developed a standardized mouse decision-making task and standardized methods for training, neural measurement, and data analysis, along with a working, scalable infrastructure for sharing data. The goal of Project 2 is to establish the causal influence of brain regions and cell types on inter-regional communication and state-dependent decision-making by integrating optogenetic perturbations at specific times during the task with simultaneous recordings of neural populations and functional ultrasound. We will consider two types of internal states: engaged/disengaged task performance and left/right biases due to the statistical structure of the environment, which varies across blocks of trials. In Aim 1, we will examine the role of subcortical structures in state-dependent decision-making with systematic optogenetic manipulations while well-trained mice perform the IBL decision task. In Aim 2, we will examine the causal effects of inhibiting target regions and/or cell types of interest on communication between other regions, using Neuropixels probes and functional ultrasound. In Aim 3, to integrate our results, we will develop dynamical computational models of multi-region population activity during our causal manipulations. These models will account for the effects of manipulation in one brain region on behavior and activity in other regions, and their dependence on internal states. The results will help interpret our experiments and refine them by suggesting other combinations of regions to record and manipulate. Together, these experiments will integrate cutting-edge experimental and computational methods to characterize the causal interactions of brainwide regions and their dependence on internal state.