Mechanisms of neural circuit dynamics in working memory

工作记忆中神经回路动力学的机制

• 批准号: 8935973
• 负责人: WILLIAM BIALEK
• 金额: $ 98.81万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8935973
• 关键词: Accounting; Achievement; Algorithms; Anatomy; Animal Model; Animals; Basal Ganglia; Beds; Behavior; Behavior monitoring; Behavioral; Behavioral Model; Brain; Brain region; Breathing; Calcium; Cataloging; Catalogs; Cells; Cerebellum; Cognition; Cognitive; Communities; Complex; Data; Decision Making; Disease; Dopamine; Electron Microscopy; Foundations; Functional disorder; Future; Generations; Goals; Head; Health; Image; Lead; Machine Learning; Maintenance; Maps; Mechanics; Memory; Methods; Microscopy; Modeling; Molecular Probes; Monitor; Neocortex; Neurons; Neurosciences; Optics; Physics; Physiological; Play; Population; Property; Psyche structure; Ramp; Reporting; Resolution; Rodent; Role; Schizophrenia; Sensory Process; Short-Term Memory; System; Technology; Testing; Time; Training; Whole-Cell Recordings; awake; base; cell type; cognitive ability; improved; in vivo; light microscopy; neural circuit; neural correlate; nonhuman primate; novel; optical imaging; optogenetics; reconstruction; relating to nervous system; response; social; theories; tool; two-photon; virtual reality

 DESCRIPTION (provided by applicant): Working memory, the ability to temporarily hold multiple pieces of information for mental manipulation, is central to virtually all cognitive abiliies. Working memory has been closely associated with multiple kinds of neural activity dynamics, such as persistent neural activity, activity ramps, and activity sequences. The neural circuit mechanisms of these dynamics remain unclear. This proposal will apply advanced technologies such as virtual reality, automated monitoring of behavior, in vivo microscopy, ontogenetic, and neural circuit reconstruction to solve fundamental problems in the understanding of working memory. The accumulation of evidence over time scales of seconds, a type of working memory critical for decision-making, will be used as a test bed for studying working memory. The proposal will build upon a rodent evidence-accumulation paradigm that allows quantitative, temporally precise parameterization of working memory and decision-making. The paradigm will be implemented with head-fixed rodents behaving in a virtual reality system (Aim 1), providing mechanical stability that enables the use of two-photon calcium imaging to observe neural activity related to working memory in the neocortex, basal ganglia, and cerebellum (Aim 3). Brain activity will also be perturbed using ontogenetic to probe the roles of brain regions and specific cell types in the formation and stabilization of memory (Aim 2). Finally, we will develop methods for probing the roles of cell types and connectivity in working memory through correlative serial electron microscopy and light microscopy as well as imaging of population responses to ontogenetic stimulation of single cells or groups of cells (Aim 4). This three-year project will produce a catalog of the types of neural circuit dynamics that are related to working memory across many brain regions. In subsequent years, this catalog will be mechanistically investigated by the anatomical and physiological methods developed in Aim 4. The long-term goal of this project is to arrive at a complete, brain-wide understanding of the cellular and circut mechanisms of activity dynamics related to working memory. The understanding is expected to take the form of a new generation of models containing cognitive variables distributed across brain regions, as well as models that explicitly represent neural circuit dynamics. This achievement will be a crucial step towards a mechanistic understanding of the neural basis of cognition.

 描述（由适用提供）：工作记忆，暂时持有多个信息进行精神操纵的能力，对于几乎所有认知障碍都是至关重要的。工作记忆与多种神经元活性动力学密切相关，例如持续的神经元活动，活性坡道和活性序列。这些动力学的神经回路机制尚不清楚。该提案将采用高级技术，例如虚拟现实，行为自动监测，体内显微镜，个体发生和神经回路的重建，以在理解工作记忆的理解中解决基本问题。秒数随时间尺度的积累，一种对决策至关重要的工作记忆的类型将被用作研究工作记忆的测试床。该提案将建立在啮齿动物证据蓄能范式的基础上，该范式允许对工作记忆和决策的临时定量，精确的参数化。该范式将通过在虚拟现实系统中表现出的头部固定啮齿动物（AIM 1）实现，提供了机械稳定性，使使用两光子钙成像可以观察到与新皮层，巴萨神经节和小脑的神经活动相关的神经活动（AIM 3）。大脑活动还将使用个体遗传学来探测大脑区域和特定细胞类型在记忆形成和稳定中的作用（AIM 2）。最后，我们将通过正确的串行电子显微镜和光学显微镜以及对单个细胞或细胞组的个体发生刺激的响应进行成像（AIM 4）来开发用于探测细胞类型和连通性在工作记忆中的作用的方法（AIM 4）。这个为期三年的项目将产生与许多大脑区域的工作记忆相关的神经回路动力学类型的目录。在随后的几年中，该目录将通过AIM 4中开发的解剖学和物理方法进行机械研究。该项目的长期目标是对与工作记忆相关的活动动态的细胞和循环机制具有完整的，全脑的了解。预计这种理解将采用新一代模型的形式，这些模型包含分布在大脑区域的认知变量，以及明确表示神经回路动力学的模型。这项成就将是朝着对认知神经元基础的机械理解的关键步骤。