Functional Organization of Grid Cells in the Entorhinal Cortex

内嗅皮层网格细胞的功能组织

• 批准号: 8243418
• 负责人: JOHN L KUBIE
• 金额: $ 25.23万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8243418
• 关键词: Affect; Alzheimer' s Disease; Behavioral; Cells; Cues; Data; Disease; Dorsal; Electrodes; Environment; Event; Floor; Goals; Head; Hippocampal Formation; Hippocampus (Brain); Individual; Lead; Learning Disorders; Light; Location; Maps; Masks; Medial; Memory; Methods; Modeling; Motion; Nature; Network-based; Pattern; Physiological; Post-Traumatic Stress Disorders; Process; Property; Qualifying; Relative (related person); Retrieval; Sensory; Slice; Slide; Space Perception; Techniques; Temporal Lobe Epilepsy; Testing; Time; Translations; Visual; Water; Work; cell behavior; cell fixing; entorhinal cortex; interest; member; novel; preference; two-dimensional; vector

DESCRIPTION (provided by applicant): The mammalian hippocampal formation is critical for memory storage and retrieval and for navigation. Over the past several decades the discoveries of place cells, head direction cells and grid cells have begun to elucidate the mechanisms for these processes. The idea has emerged that the hippocampal formation creates a rigid, two-dimensional framework upon which specific objects, places and events can be registered. The registration of sensory data on the inherent framework appears to be critical for both memory and navigation. Grid cells of the medial entorhinal cortex are the core of the proposed framework. The spatial firing pattern of a single grid cell, with bumps distributed at regular distances from one another and patterned in a triangular lattice, suggests the nature of the 2D representation. While we have begun to understand the nature of individual grid cells, little is known about how grid cells within medial entorhinal cortex relate and connect to one another to form a network. Emerging evidence suggests that within a small region of entorhinal cortex grid cells form a "module" where all of the cells have identical scale and orientation. While it is clear that this is roughly true for broad regions, it is not clear if there are what we call "rigid modules": that is, sets of grid cells with identical scale and orientation, where the spatial offsets among members are fixed across all environments. Characterization of the modular organization of the entorhinal cortex is a critical step in elucidating the inherent framework that is the core of hippocampal processing. Characterizing modules is the goal of the proposed studies. The first group of studies (strategic aims 1) is aimed at mapping hippocampal modules and exploring the extent that the modules may be rigid. We will make simultaneous recordings of grid cells within a small region (off of single tetrodes) and across broader regions (across tetrodes) to see whether the grid scale and orientations of the simultaneously recorded cells are fixed locally or across broader regions. Since we are particularly interested in whether pairs of cells are part of a rigid set, we will explore whether the spatial offsets of their grid bumps are fixed across broad regions of environmental space and across environments. The second study (strategic aim 2) will make a critical test for the existence of rigid modules. The strategy is to create a situation where grid cell firing drifts, due to lack of sensory cues, and to see whether firing patterns are maintained and pairs of grid cells drift together. Part one involves creating a sensory-deprived environment and establishing that it is sufficient to get reliable grid-cell drift. In part 2 we will control for drift and see whether within and across cell firing patterns remain stable and rigid. PUBLIC HEALTH RELEVANCE: Normal functioning of the hippocampus is critical for navigation and memory. Understanding processing within the hippocampal formation may shed light on disorders involving the hippocampal formation and lead to the treatment of these disorders. Disorders and diseases that affect the hippocampus include Alzheimer's disease, temporal lobe epilepsy, post-traumatic stress disorder and learning disorders.

描述(申请人提供)：哺乳动物的海马体结构对于记忆的存储和检索以及导航都是至关重要的。在过去的几十年里，位置细胞、头向细胞和网格细胞的发现已经开始阐明这些过程的机制。出现了一个想法，即海马体结构创建了一个刚性的二维框架，在其上可以登记特定的对象、地点和事件。感觉数据在固有框架上的注册似乎对记忆和导航都至关重要。内侧内嗅觉皮质的网格细胞是拟议框架的核心。单个网格单元的空间激发模式，凸起以规则的距离分布，并在三角形网格中形成图案，表明了2D表示的性质。虽然我们已经开始了解单个网格细胞的性质，但对于内侧内嗅皮层中的网格细胞如何联系并相互连接以形成网络，我们知之甚少。新出现的证据表明，在内嗅皮层的一小块区域内，网格细胞形成了一个“模块”，其中所有细胞的规模和方向都相同。虽然很明显，这大致适用于广泛的区域，但尚不清楚是否存在我们所称的“刚性模块”：即具有相同比例和方向的网格单元集，其中成员之间的空间偏移量在所有环境中是固定的。内嗅皮层的模块化组织的特征是阐明作为海马处理核心的内在框架的关键一步。刻画模块是所提出的研究的目标。第一组研究(战略目标1)旨在绘制海马区模块图，并探索这些模块可能僵化的程度。我们将在小区域内(单个四极管)和跨较大区域(跨四极管)同时记录网格单元，以查看同时记录的单元的网格比例和方向是局部固定的还是跨较大区域固定的。由于我们特别感兴趣的是细胞对是否是刚性集合的一部分，我们将探索它们的网格凹凸的空间偏移量是否在广泛的环境空间区域和跨环境中是固定的。第二个研究(战略目标2)将对刚性模块的存在进行关键测试。其策略是创造一种情况，即由于缺乏感觉线索，网格细胞的放电会发生漂移，并观察放电模式是否保持，成对的网格细胞一起漂移。第一部分涉及创造一种感觉缺失的环境，并确定获得可靠的网格细胞漂移就足够了。在第二部分中，我们将控制漂移，看看细胞内和细胞间的放电模式是否保持稳定和僵化。 与公共健康相关：海马体的正常功能对导航和记忆至关重要。了解海马体结构内的过程可能有助于了解涉及海马体结构的疾病，并导致这些疾病的治疗。影响海马体的障碍和疾病包括阿尔茨海默氏症、颞叶癫痫、创伤后应激障碍和学习障碍。