Causal brainwide interactions underlying internal states and decisions

摘要/摘要，项目2 即使在相同的环境中，动物在不同的场合也可能做出不同的决定，因为它 内部状态，如参与一项任务，与外部输入有力地相互作用，以确定行为。 该提案的首要目标是了解内部状态如何影响决策，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， 该联盟已经开发了标准化的小鼠决策任务和标准化的方法， 训练、神经测量和数据分析，沿着一个有效的、可扩展的基础设施，用于共享数据。 项目2的目标是建立大脑区域和细胞类型对区域间的因果影响。 通过整合特定时间的光遗传学扰动进行通信和状态依赖性决策 同时记录神经群和功能超声。我们会考虑 两种类型的内部状态：参与/脱离任务绩效和左/右偏见，由于统计 环境的结构，这在不同的试验块。在目标1中，我们将研究皮层下的作用， 结构的状态依赖性决策与系统的光遗传学操作，而训练有素的小鼠 执行IBL决策任务。在目标2中，我们将检查抑制靶区域和/或细胞的因果效应。 使用Neuropixels探头和功能性超声，对其他区域之间的通信感兴趣的类型。 在目标3中，为了整合我们的研究结果，我们将建立多区域种群的动力学计算模型 在我们的因果操纵过程中。这些模型将解释在一个大脑中操纵的影响 区域对其他区域的行为和活动的影响，以及它们对内部状态的依赖。这些结果将帮助 解释我们的实验，并通过建议记录和操作的其他区域组合来完善它们。 总之，这些实验将整合尖端的实验和计算方法， 全脑区域的因果互动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.