Mechanisms of neural circuit dynamics in working memory anddecision-making

工作记忆和决策中的神经回路动力学机制

• 批准号: 9983177
• 负责人: Carlos D Brody
• 金额: $ 306.24万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-28 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9983177
• 关键词: Achievement; Alzheimer' s Disease; Anatomy; Animals; Area; Atlases; Attention deficit hyperactivity disorder; Automation; Back; Basic Science; Behavior; Behavioral; Biological Assay; Biophysics; Bipolar Depression; Brain; Brain region; Calcium; Cerebellum; Code; Cognition; Collaborations; Complex; Computing Methodologies; Data; Data Science; Data Set; Decision Making; Dementia; Disease; Dorsal; Electrophysiology (science); Experimental Designs; Goals; Human Resources; Image; Individual; Location; Machine Learning; Maps; Methods; Microscopy; Mind; Modeling; Molecular Probes; Monitor; Neurons; Optics; Pathway interactions; Physiologic pulse; Physiological; Population; Process; Psyche structure; Quality Control; Research; Research Personnel; Research Project Grants; Research Support; Resolution; Resources; Rodent; Running; Schizophrenia; Sensory; Short-Term Memory; Statistical Data Interpretation; Statistical Methods; System; Techniques; Technology; Testing; Therapeutic; Training; Ventral Tegmental Area; Work; autism spectrum disorder; base; cell type; cognitive ability; cognitive process; cost effectiveness; data to knowledge; design; experimental study; imaging modality; improved; information processing; instrumentation; large scale data; member; network models; neural circuit; neuromechanism; new technology; optogenetics; reconstruction; relating to nervous system; scale up; social computing; tool; two-photon; virtual; virtual reality

Project Summary Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is central to virtually all cognitive abilities. Recent technical advances have opened an unprecedented opportunity to comprehensively dissect the neural circuit mechanisms of this ability across multiple brain areas. The task to be studied is a common form of decision-making that is based on the gradual accumulation of sensory evidence and thus relies on working memory. A team of leading experts propose to investigate the neural basis of this behavior using the latest techniques, including virtual reality, high-throughput automated behavioral training, large-scale cellular-resolution imaging in behaving rodents, manipulation of neural activity in specific brain areas and cell types, and automated anatomical reconstruction. In particular, the researchers will identify key brain regions that are required for this decision task through systematic, temporally specific inactivations via optogenetics technology, across all of dorsal cortex and in key subcortical areas, and use quantitative model-fitting to evaluate the effects. They will use state-of-the-art two-photon calcium imaging methods and electrophysiology to characterize the information flow in many individual neurons within these brain areas during the task. In addition, they will use cutting-edge anatomical reconstructions and new functional connectivity methods, within and across brain regions, to evaluate the interactions of these physiologically characterized neurons. The long-term goal of this project is to arrive at a complete, brain-wide understanding of the cellular and circuit mechanisms of activity dynamics related to working memory. Finally, they will use sophisticated computational methods to incorporate this new understanding into a realistic circuit model that will support a tightly integrated process of model-guided experimental design, in which the model suggests the most informative experiments and their results are then fed back to improve the model’s fidelity. This process is expected to produce the most accurate and detailed multi-brain-region biophysical circuit model of a cognitive process in existence. In addition, the proposed research will enable researchers to generate and test a variety of hypotheses about the neural basis of evidence accumulation, working memory, and decision-making. Taken together, these achievements will represent a crucial step toward a mechanistic understanding of how the brain works with information.

项目摘要 工作记忆，暂时牢记多个信息进行操作的能力是 几乎所有认知能力的核心。最近的技术进步已经开放了前所未有的 有机会全面剖析多个大脑的这种能力的神经回路机制 区域。要研究的任务是一种基于等级的决策的常见形式 感觉证据的积累，因此依赖于工作记忆。一支领先的专家团队提议 使用最新技术（包括虚拟现实）来研究这种行为的神经元基础 高通量自动行为训练，行为啮齿动物中的大规模细胞分辨率成像， 在特定的大脑区域和细胞类型中操纵神经活动，并自动解剖 重建。特别是，研究人员将确定该决定所需的关键大脑区域 通过光遗传学技术通过系统的，暂时特定的灭绝任务，在所有背侧 皮质和关键皮层区域，并使用定量模型拟合来评估效果。他们会使用 最先进的两光子钙成像方法和电生理学来表征信息 任务期间，这些大脑区域内许多单个神经元的流动。此外，他们将使用 尖端的解剖重建和新的功能连接方法在大脑内外 区域，以评估这些物理表征的神经元的相互作用。长期目标 该项目将对细胞和电路机制有完整的脑部了解 活动动态与工作记忆有关。最后，他们将使用复杂的计算方法 将这种新的理解纳入了现实的电路模型，该模型将支持紧密整合 模型引导的实验设计过程，其中模型提出了最有用的信息 然后将实验及其结果反馈，以提高模型的保真度。期望这个过程 产生认知过程中最准确，最详细的多脑区域生物物理电路模型 存在。此外，拟议的研究将使研究人员能够生成和测试各种 关于证据积累，工作记忆和决策的神经基础的假设。 综上所述，这些成就将代表着对机械理解的关键一步 大脑与信息一起工作。