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A Control Theoretic Approach to Addressing Hippocampal Function

解决海马功能的控制理论方法

基本信息

批准号：
9128055
负责人：
Noah John Cowan
金额：
$ 24.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9128055
关键词：
Address Alzheimer&apos s Disease Animals Area Behavior Binding Biological Models Brain Breathing Cells Characteristics Cognition Cognitive Collaborations Conscious Cues Development Disadvantaged Disease Dissociation Elements Engineering Environment Episodic memory Event Feedback Foundations Goals Hallucinations Health Hippocampal Formation Hippocampus (Brain)Individual Investigation Knowledge Learning Location Maps Memory Memory Loss Mental disorders Modeling Motion Motor Movement Neurobiology Neurodegenerative Disorders Neurons Neurosciences Optics Pattern Perception Physical Restraint Pilot Projects Population Positioning Attribute Problem Solving Procedures Process Protocols documentation Rattus Research Schizophrenia Sensory Signal Transduction Speed Stroke System Systems Integration Systems Theory Techniques Technology Testing Thinking Time Update Vision Visual Work base biological systems cognitive control design design and construction dynamic system entorhinal cortex episodic like memory expectation experience insight nervous system disorder neuromechanism neurophysiology novel novel strategies optical imaging phenomenological models programs relating to nervous system research study sensory input spatial relationship spatiotemporal vector virtual reality visual feedback

项目摘要

DESCRIPTION (provided by applicant): 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 that caused a graceful, coherent dissociation of the place ﬁelds from the landmarks. We will test the capacity of the system to recalibrate the path integrator when challenged with this sustained conﬂict. Further, we will develop a novel approach for isolating the contribution of optic ﬂow and other selfmotion cues to the update of the neural representation of position, free of the competing inﬂuence of landmarks. Speciﬁcally, we will attempt to decode and control this cognitive representation during behavior through realtime 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 may reveal important principles of neural computation relevant to general problems of how the brain integrates external sensory input with internal, cognitive representations, and may generate insights into the disordered thinking and hallucinations that are characteristic of schizophrenia and other mental disorders.

描述(申请人提供)：海马体结构与学习和记忆密切相关。阿尔茨海默病等神经退行性疾病极大地影响了这一区域，导致严重的进行性记忆丧失。海马体似乎是外部世界的一个以分配为中心的认知地图的中心。这张地图不仅对空间认知至关重要，对有意识地回忆过去的经历也是至关重要的。海马体被认为在一个连贯的时空框架内将经验的个体项目和事件联系在一起，允许经验作为有意识的记忆被存储和检索。几十年来对海马区细胞的研究和最近发现的网格细胞表明，这一认知图谱来自外部感觉输入和内源性神经动力学的相互作用(基于被称为路径整合的导航策略)。对行为动物的经典神经生理学研究已经充分表征了这些空间细胞的ﬂ环位置上的环境标志的强大作用。将这一方法扩展到定量研究PATH的内部过程事实证明，整合在技术上具有挑战性。虚拟现实技术与系统论相结合，为解决这些问题提供了契机。我们设计并构建了一种新颖的设备，它允许我们操纵大鼠在真实圆形轨道上导航时可获得的视觉输入(地标和光学ﬂow)，作为其运动的函数，同时保持正常的行走和前庭体验。在该装置中记录的放置细胞复制了已知的标准现象。在初步实验中，我们在地标信息和路径整合之间诱导了持续的、不断增加的ﬂICT，这导致了Placeﬁ区域与地标的优雅、连贯的分离。我们将测试系统重新校准路径集成器的能力，以应对这一持续的ﬂICT挑战。此外，我们将开发一种新的方法来分离光学ﬂow和其他自运动线索对位置的神经表征更新的贡献，而不是地标的竞争ﬂuence。具体地说，我们将试图通过实时操纵视觉ﬁﬂ来解码和控制行为过程中的这种认知表征。这种方法将形成一个新的研究计划的基础，旨在全面分析认知地图的外部和内部决定因素。此外，该程序可能揭示与大脑如何将外部感觉输入与内部认知表征相结合的一般问题相关的神经计算的重要原理，并可能对精神分裂症和其他精神障碍的特征思维障碍和幻觉产生洞察力。