Functional Organization of Grid Cells in the Entorhinal Cortex

描述（申请人提供）：哺乳动物海马的形成是记忆存储和检索和导航的关键。在过去的几十年里，位置细胞、头部方向细胞和网格细胞的发现已经开始阐明这些过程的机制。海马体的形成形成了一个刚性的二维框架，在这个框架上可以记录特定的物体、地点和事件。在固有框架上注册感官数据似乎对记忆和导航都至关重要。内嗅皮层的网格细胞是提出的框架的核心。单个网格细胞的空间发射模式，其凸起分布在彼此之间的规则距离上，并在三角形晶格中形成图案，表明了二维表示的本质。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相互关联并相互连接以形成一个网络，我们知之甚少。新出现的证据表明，在内嗅皮层的一个小区域内，网格细胞形成了一个“模块”，其中所有的细胞都具有相同的规模和方向。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谓的“刚性模块”：即具有相同规模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都是固定的。表征的模块化组织的内嗅皮层是阐明内在框架的关键一步，是海马处理的核心。表征模块是拟议研究的目标。第一组研究（战略目标1）旨在映射海马模块并探索模块可能是刚性的程度。我们将同时记录小区域内的网格细胞（在单个四极上）和更大区域内的网格细胞（在四极上），以查看同时记录的网格细胞的尺度和方向是在局部固定还是在更大的区域固定。由于我们对细胞对是否是刚性集合的一部分特别感兴趣，因此我们将探索它们的网格凸起的空间偏移是否在环境空间和环境的广泛区域中是固定的。第二项研究（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，使网格细胞的放电由于缺乏感官线索而漂移，并观察放电模式是否维持，以及成对的网格细胞是否一起漂移。第一部分包括创造一个感官被剥夺的环境，并确定它足以获得可靠的网格细胞漂移。在第2部分中，我们将控制漂移，并查看细胞内部和细胞之间的放电模式是否保持稳定和刚性。

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.