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，内部大脑状态 我们合作的最新工作表明，啮齿动物的感官决策依赖 时变的内部状态，在不同州采用了不同的决策策略。我们有 开发了一个统计模型，可以单独从决策行为中识别这些州，并发现 小鼠在数十个时期的策略之间转换为数百个任务试验。这一发现提出了专业 挑战传统的决策模型，假设训练有素的动物依靠一个 在会议中相对固定的证据蓄能策略。此外，我们发现失活 纹状体仅在某些州影响动物的选择；在其他州，决策不受 纹状体失活，表明小鼠依靠不同的神经回路来在不同状态下做出决策。 该项目将跟进这一开始发现，以调查基础神经机制 整个大脑的内部状态。 AIM 1将专注于表征内部控制感官的神经基础 决策和工作记忆。我们将使用因果扰动和大规模神经记录 表征种群活动在各州之间的变化，并使用闭环光学灭活 实验以检查不同状态中不同大脑区域如何有助于决策。 AIM 2将在大脑内部看，以从神经活动的动力学中识别内部状态。我们将 开发新模型来表征内部状态在使用Spike的单个试验时间尺度上演变的方式 火车数据。然后，我们将使用这些模型来表征大脑之间的状态依赖性通信 大规模多区域电生理记录中的区域。 AIM 3将专注于确定与模型相关的认知决策状态如何确定 生理定义的内部状态，例如口渴，饥饿和唤醒。这将使我们能够联系我们的 有关物理内部状态的广泛文献的决策策略的发现。分析 唤醒，我们将测量瞳孔直径并使用纤维光度法来测量去甲肾上腺素能的活性 基因座基因座和胆碱能神经元中的神经元中的基本前脑中的神经元。作为饥饿和 第三，我们将测量相关下丘脑神经元种群中的活动。这些测量将是 与我们的模型中得出的内部状态相比。 我们希望该项目的实验和建模工作将大大提高两个优先级 大脑倡议的领域：证明因果关系并确定基本原则。