Functional Organization of Grid Cells in the Entorhinal Cortex

描述（由申请人提供）：哺乳动物海马结构对于记忆存储和检索以及导航至关重要。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。人们认为，海马结构创建了一个严格的二维框架，可以在该框架上记录特定的物体、地点和事件。感知数据在固有框架上的注册似乎对于记忆和导航都至关重要。内侧内嗅皮层的网格细胞是所提出框架的核心。单个网格单元的空间发射图案（凸块彼此间隔一定距离分布并以三角形晶格图案化）表明了二维表示的本质。虽然我们已经开始了解各个网格细胞的性质，但我们对内侧内嗅皮层内的网格细胞如何相互关联和连接以形成网络知之甚少。新的证据表明，在内嗅皮层的一小块区域内，网格细胞形成一个“模块”，其中所有细胞都具有相同的尺度和方向。虽然很明显这对于广泛的区域来说大致如此，但尚不清楚是否存在我们所说的“刚性模块”：即具有相同规模和方向的网格单元组，其中成员之间的空间偏移在所有环境中都是固定的。内嗅皮层模块化组织的表征是阐明海马处理核心固有框架的关键步骤。表征模块是拟议研究的目标。第一组研究（战略目标 1）旨在绘制海马模块图并探索这些模块可能的刚性程度。我们将同时记录小区域内（单个四极管之外）和更广泛区域（跨四极管）内的网格单元，以查看同时记录的单元格的网格比例和方向是否在本地或跨更广泛的区域固定。由于我们特别感兴趣的是成对的单元是否是刚性集合的一部分，因此我们将探索它们的网格凹凸的空间偏移是否在广泛的环境空间区域和跨环境中是固定的。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。该策略是创造一种由于缺乏感觉线索而导致网格细胞放电漂移的情况，并观察放电模式是否得到维持以及成对的网格细胞是否一起漂移。第一部分涉及创建一个感觉剥夺的环境，并确定它足以获得可靠的网格单元漂移。在第 2 部分中，我们将控制漂移并查看细胞内和细胞间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.