P3: Internal Brain States

P3：大脑内部状态

• 批准号: 10705965
• 负责人: Jonathan William Pillow
• 金额: $ 38.23万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-08 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705965
• 关键词: Affect; Animals; Area; Arousal; BRAIN initiative; Behavior; Behavioral; Biological Assay; Brain; Brain region; Cognitive; Collaborations; Communication; Corpus striatum structure; Data; Data Science; Data Set; Decision Analysis; Decision Making; Dependence; Diameter; Electrophysiology (science); Etiology; Exhibits; Fiber; Funding; Geometry; Hunger; Hypothalamic structure; Literature; Measurement; Measures; Memory; Modeling; Mus; Neuroanatomy; Neurons; Nonlinear Dynamics; Optics; Outcome; Photometry; Physiological; Physiology; Population; Pupil; Rodent; Sensory; Short-Term Memory; Signal Transduction; Statistical Models; Structure; Testing; Thirst; Time; Training; Work; basal forebrain; biophysical model; cholinergic neuron; experimental study; follow-up; locus ceruleus structure; neural; neural circuit; neuromechanism; noradrenergic; optogenetics; theories; tool

Summary/Abstract: Project 3, Internal Brain States Recent work from our collaboration has revealed that sensory decision-making in rodents relies on time-varying internal states, with distinct decision-making strategies employed in different states. We have developed a statistical model for identifying these states from decision-making behavior alone, and find that mice switch among strategies on the timescale of tens to hundreds of task trials. This finding presents a major challenge to traditional models of decision-making, which assume that trained animals rely on a single evidence-accumulation strategy that is relatively fixed within a session. Furthermore, we found that inactivation of the striatum affects the animal’s choices only in some states; in other states, decisions are not affected by striatal inactivation, suggesting that mice rely on distinct neural circuits for making decisions in different states. This project will follow up on this startling discovery in order to investigate the neural mechanisms underlying internal states throughout the brain. Aim 1 will focus on characterizing the neural basis for the internal states governing sensory decision-making and working memory. We will use causal perturbations and large-scale neural recordings to characterize how population activity varies across states, and use closed-loop optogenetic inactivation experiments to examine how different brain regions contribute to decision-making in different states. Aim 2 will look inside the brain to identify internal states from the dynamics of neural activity. We will develop new models to characterize how internal states evolve on the timescale of single trials using spike train data. We will then use these models to characterize state-dependent communication between brain regions in large-scale multi-region electrophysiological recordings. Aim 3 will focus on determining how the cognitive decision-making states identified by our model relate physiologically-defined internal states such as thirst, hunger, and arousal. This will allow us to connect our findings about decision-making strategies to the extensive literature on physiological internal states. To assay arousal, we will measure pupil diameter and use fiber photometry to measure activity of noradrenergic neurons in the locus coeruleus and cholinergic neurons in basal forebrain. As a neural readout of hunger and thirst, we will measure activity in relevant hypothalamic neuron populations. These measurements will be compared to internal states derived from our models. We expect the experiments and modeling efforts in this project to substantially advance two priority areas of the BRAIN Initiative: demonstrating causality and identifying fundamental principles.

摘要/摘要：项目3，大脑内部状态 我们合作的最新研究表明，啮齿动物的感官决策依赖于 内部状态时变，不同状态采用不同的决策策略。我们有 开发了一个统计模型，仅从决策行为中识别这些状态，并发现 小鼠在数十到数百次任务试验的时间尺度上切换策略。这一发现提出了一个重大的 挑战传统的决策模式，这种模式假设经过训练的动物依赖于单一的 一次会议中相对固定的证据积累策略。此外，我们发现灭活 纹状体的变化只在某些状态下影响动物的选择；在其他状态下，决定不受 纹状体失活，这表明小鼠在不同的状态下依靠不同的神经回路做出决定。 该项目将在这一惊人发现的基础上进一步研究 整个大脑的内部状态。 目标1将重点描述支配感觉的内部状态的神经基础 决策和工作记忆。我们将使用因果扰动和大规模神经记录来 表征种群活动在各州之间的变化，并使用闭合环光遗传失活 研究不同大脑区域如何在不同状态下对决策做出贡献的实验。 目标2将研究大脑内部，从神经活动的动力学中识别内部状态。我们会 使用SPEKE开发新的模型来描述内部状态如何在单次试验的时间尺度上演变 列车数据。然后，我们将使用这些模型来描述大脑之间的状态依赖通信 大规模多区域电生理记录中的区域。 目标3将侧重于确定我们的模型所确定的认知决策状态之间的关联 生理定义的内部状态，如口渴、饥饿和觉醒。这将使我们能够将我们的 对有关生理内部状态的大量文献的决策策略的研究结果。进行化验 觉醒时，我们将测量瞳孔直径，并使用纤维光度法测量去甲肾上腺素的活性 蓝斑神经元和基底前脑胆碱能神经元。作为饥饿和饥饿的神经读数 口渴时，我们将测量相关下丘脑神经元群的活动。这些测量结果将是 与由我们的模型得出的内部状态相比。 我们预计这个项目中的实验和建模工作将大大推进两个优先事项 大脑倡议的领域：展示因果关系和确定基本原则。