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

项目总结 海马体结构与学习和记忆密切相关。神经退行性疾病，如 阿尔茨海默氏症极大地影响了这一区域，导致严重的进行性记忆丧失。这个 海马体似乎是外部世界的一个分位性认知地图的位置。这张地图很关键 不仅是为了空间认知，也是为了有意识地回忆过去的经历。海马体是 认为将个体体验项目和事件绑定在连贯的时空框架内， 从而允许将体验作为有意识的记忆来存储和检索。数十年的调查研究 海马区细胞和最近发现的网格细胞揭示了这种认知图谱起源于 外部感觉输入与内源性神经动力学的相互作用(潜在的 称为“路径整合”的导航策略)。关于行为动物的经典神经生理学研究 充分描述了环境地标对这些射击地点的强大影响 空间单元格。将这一方法扩展到定量研究路径整合的内部过程 事实证明，这在技术上具有挑战性。虚拟现实技术，与系统论相结合，提供了机会 来解决这些问题。我们已经设计和建造了一种新颖的设备，它允许我们操纵 视觉输入(包括地标和光流)可供大鼠在真实圆形轨道上导航时使用，这取决于其 运动，同时保持正常的行走和前庭体验。放置记录在此中的单元格 仪器复制了已知的标准现象学。在初步实验中，我们诱导了一种持续的， 地标信息与路径整合之间的冲突日益加剧。结果表明， 系统在遇到这种持续冲突时重新校准路径集成器。此外，我们还开发了 分离光流和其他自运动线索对神经更新的贡献的一种新方法 代表位置，不受地标的竞争影响。具体地说，我们开发了一种 在线种群解码器，并在行为过程中使用解码的输出来控制这种认知表征 通过对光流的实时反馈操作。这种方法将构成一部小说的基础 旨在全面分析认知的外部和内部决定因素的研究计划 地图。此外，该程序承诺揭示与一般神经计算相关的重要原理。 大脑最终如何将外部感觉输入与内部认知表征相结合的问题 对精神分裂症和精神分裂症的思维紊乱和幻觉有深入的了解 其他精神障碍。 1