A Control Theoretic Approach to Addressing Hippocampal Function

 描述（由申请人提供）：海马结构与学习和记忆密切相关。神经退行性疾病，如阿尔茨海默病，严重影响这一领域，导致严重和渐进的记忆丧失。海马体似乎是外部世界的非自我中心的认知地图的所在地。这张地图不仅对空间认知至关重要，而且对过去经验的有意识回忆也至关重要。海马体被认为将个体项目和经验事件绑定在一个连贯的时空框架内，允许经验作为有意识的记忆被存储和检索。几十年来对海马位置细胞的研究和最近对网格细胞的发现表明，这种认知地图是由外部感觉输入与内源性神经动力学（称为“路径整合”的导航策略）的相互作用产生的。对行为动物的经典神经生理学研究已经充分描述了环境地标对这些空间细胞放电位置的强大影响。将此方法扩展到定量研究路径的内部过程 集成在技术上具有挑战性。虚拟现实技术与系统理论的结合为解决这些问题提供了契机。我们已经设计并构建了一种新的装置，使我们能够操纵视觉输入（地标和视觉流）提供给大鼠导航真实的圆形轨道作为其运动的功能，同时保持正常的走动和前庭经验。将记录的细胞放置在该装置中复制已知的标准现象学。在初步实验中，我们在地标信息和路径整合之间引发了持续的、不断增加的冲突，导致了地点场与地标的优雅、连贯的分离。我们将测试系统在受到这种持续冲突的挑战时重新校准路径积分器的能力。此外，我们将开发一种新的方法来隔离的贡献的视觉反射和其他自我运动线索的更新的神经表征的位置，免费的竞争中的里程碑。具体来说，我们将试图通过实时操纵视觉神经，在行为过程中解码和控制这种认知表征。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与内部决定因素。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整合的一般问题相关的神经计算的重要原理，并可能产生对精神分裂症和其他精神障碍特征的思维障碍和幻觉的见解。

 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.