A Control Theoretic Approach to Addressing Hippocampal Function

解决海马功能的控制理论方法

• 批准号: 9364446
• 负责人: Noah John Cowan
• 金额: $ 41.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9364446
• 关键词: Address; Alzheimer' s Disease; Animals; Anterior; Area; Behavior; Binding; Biological Models; Brain; Cell Nucleus; Cells; Characteristics; Cognition; Cognitive; Conflict (Psychology); Conscious; Cues; Disease; Dorsal; Elements; Engineering; Environment; Event; Feedback; Foundations; Hallucinations; Head; Hippocampal Formation; Hippocampus (Brain); Individual; Investigation; Learning; Location; Locomotion; Maps; Measurable; Memory; Memory Loss; Mental disorders; Modeling; Motion; Motor; Movement; Neurobiology; Neurodegenerative Disorders; Neurosciences; Output; Perception; Plasticizers; Population; Positioning Attribute; Problem Solving; Process; Rattus; Research; Rodent; Role; Schizophrenia; Sensory; Series; Signal Transduction; Source; Speed; Stroke; System; Systems Integration; Systems Theory; Technology; Testing; Thalamic structure; Thinking; Time; Training; Update; Vision; Visual; cognitive control; design and construction; episodic like memory; expectation; experience; experimental study; insight; nervous system disorder; neuromechanism; neurophysiology; novel; novel strategies; optic flow; phenomenological models; prevent; programs; relating to nervous system; sensory input; spatial relationship; spatiotemporal; vector; virtual reality; visual control; visual feedback

PROJECT SUMMARY The hippocampal formation is critically involved in learning and memory. Neurodegenerative disorders such as Alzheimer’s Disease dramatically impact this area, leading to severe and progressive memory loss. The hippocampus appears to be the locus of an allocentric, cognitive map of the external world. This map is critical not only for spatial cognition, but also for the conscious recollection of past experience. The hippocampus is thought to bind the individual items and events of experience within a coherent spatiotemporal framework, allowing the experience to be stored and retrieved as a conscious memory. Decades of investigation of hippocampal place cells and the recent discovery of grid cells have revealed that this cognitive map arises from the interaction of external sensory inputs with endogenously generated neural dynamics (underlying the navigational strategy known as “path integration”). Classical neurophysiological studies with behaving animals have amply characterized the powerful influence of environmental landmarks on the firing locations of these spatial cells. Extending this approach to quantitatively investigate the internal processes of path integration has proven technically challenging. Virtual reality technology, in combination with systems theory, offers opportunities to solve these problems. We have designed and constructed a novel apparatus that allows us to manipulate the visual inputs (both landmarks and optic flow) available to a rat navigating a real circular track as a function of its movements, while preserving normal ambulatory and vestibular experience. Place cells recorded in this apparatus replicate known standard phenomenology. In preliminary experiments, we induced a sustained, increasing conflict between landmark information and path integration. Results demonstrate the capacity of the system to recalibrate the path integrator when challenged with this sustained conflict. Further, we have developed a novel approach for isolating the contribution of optic flow and other self-motion cues to the update of the neural representation of position, free of the competing influence of landmarks. Specifically, we have developed an online population decoder, and used the decoded output to control this cognitive representation during behavior through real-time feedback manipulations of the optic flow. This approach will form the foundation of a novel research program aimed at a comprehensive analysis of the external vs. internal determinants of the cognitive map. Furthermore, this program promises to reveal important principles of neural computation relevant to general problems of how the brain integrates external sensory input with internal, cognitive representations, ultimately generating insights into the disordered thinking and hallucinations that are characteristic of schizophrenia and other mental disorders. 1

项目概要 海马结构与学习和记忆等神经退行性疾病密切相关。 阿尔茨海默氏病极大地影响了该区域，导致严重且进行性的记忆丧失。 海马体似乎是外部世界的非中心认知地图的所在地，这张地图至关重要。 海马体不仅负责空间认知，还负责有意识地回忆过去的经历。 被认为将单个项目和经验事件绑定在一个连贯的时空框架内， 允许将经验作为数十年的有意识的记忆进行存储和检索。 海马位置细胞和最近发现的网格细胞表明，这种认知图源于 外部感觉输入与内源性产生的神经动力学的相互作用（在 称为“路径整合”的导航策略）。 充分描述了环境地标对这些发射地点的强大影响 扩展这种方法来定量研究路径整合的内部过程。 事实证明，虚拟现实技术与系统理论相结合，具有技术挑战性，提供了机会。 为了解决这些问题，我们设计并建造了一种新颖的装置，使我们能够操纵 老鼠在真实的圆形轨道上导航时可获得的视觉输入（地标和光流）作为其 运动，同时保留在此记录的正常行走和前庭体验。 仪器复制了已知的标准现象学。在初步实验中，我们诱导了持续的、 地标信息和路径整合之间的冲突不断增加。结果证明了系统的能力。 此外，我们还开发了一种系统，用于在面临这种持续冲突的挑战时重新校准路径积分器。 一种新颖的方法，用于隔离光流和其他自运动线索对神经网络更新的贡献 具体来说，我们开发了一种位置表示，不受地标的竞争影响。 在线群体解码器，并使用解码的输出来控制行为过程中的认知表征 通过光流的实时反馈操纵，这种方法将构成一种新颖的基础。 研究计划旨在全面分析认知的外部与内部决定因素 此外，该程序有望揭示与一般相关的神经计算的重要原理。 大脑如何将外部感觉输入与内部认知表征整合起来的问题 深入了解精神分裂症特有的思维混乱和幻觉， 其他精神障碍。 1