CRCNS: Path Integration by the Grid Cell Network

描述(申请人提供)：海马体中的记忆电路对于存储和检索有关我们生活经历的信息至关重要，使我们能够构建对我们周围世界的准确表征--这是正常认知和行为的基本要求。海马体记忆回路的功能障碍会导致毁灭性的记忆障碍、认知错误、痴呆症和精神病，这些都是精神分裂症、阿尔茨海默病和其他精神障碍的常见精神症状。为了开发更好的治疗这些疾病的方法，了解支持海马体学习和记忆的细胞计算是必不可少的。侵入性神经生理学实验不能在人类身上进行，因此关于细胞记忆机制的许多已知知识都是从动物模型中了解到的，特别是啮齿动物。啮齿动物非常善于学习如何在熟悉的区域内导航，这些能力依赖于大脑海马区和海马区旁的空间记忆回路(就像人类一样)。啮齿动物的海马体含有被称为“定位细胞”的神经元，当动物访问特定位置时，这些神经元选择性地被激活，为编码熟悉的空间环境的记忆表征提供了神经底物。然而，位置细胞如何处理来自海马体以外的传入信号来编码空间记忆，目前还不是很清楚。最近，人们发现大鼠的内嗅觉皮质含有一群以前不为人知的神经元，称为“网格细胞”。当一只老鼠在一个空间环境中导航时，网格细胞在多个位置选择性地发射，形成一个六边形的网格图案，以惊人的几何精度铺设环境的表面。内嗅觉网格细胞向海马区细胞发送密集的投射，这表明网格细胞可能提供了海马体构建空间记忆表征的基本构件。本文提出的研究将结合理论建模研究、神经生理学记录和清醒大鼠的损毁实验，研究网格细胞是如何产生其显著的六角形发射场的，以及这些发射场如何作为构建海马记忆表征的计算基础。这一跨学科的研究计划具有巨大的潜力，可以彻底改变我们对皮质-海马体相互作用的理解，揭示皮质是如何将传入的关于世界的感觉信息打包成一种形式，海马体可以利用这种形式来构建熟悉位置、物体和事件的连贯记忆表征。从这些研究中获得的知识可能会开启一个新的发现时代，从而带来减轻精神障碍患者认知和记忆缺陷负担的新疗法。

DESCRIPTION (provided by applicant): Memory circuits in the hippocampus are critical for storing and retrieving information about our life experiences, allowing us to construct accurate representations of the world around us-a basic requirement for normal cognition and behavior. Dysfunction of hippocampal memory circuits can lead to devastating memory impairments, errors of cognition, dementia, and psychosis which are common psychiatric symptoms of schizophrenia, Alzheimer's disease, and other mental disorders. To develop better treatments for these conditions, it is essential to understand the cellular computations that support learning and memory in the hippocampus. Invasive neurophysiological experiments cannot be performed in humans, so much of what is known about cellular memory mechanisms has been learned from animal models, especially rodents. Rodents are very good at learning to navigate through familiar territories, and these abilities depend upon spatial memory circuits within the hippocampal and parahippocampal regions of the brain (as in humans). The rodent hippocampus contains neurons called "place cells" that fire selectively when the animal visits specific locations, providing a neural substrate for encoding memory representations of familiar spatial environments. However, it is not well understood how incoming signals from outside the hippocampus are processed by place cells to encode spatial memories. Very recently, it has been discovered that the rat entorhinal cortex contains a previously unknown population of neurons called "grid cells." As a rat navigates through a spatial environment, grid cells fire selectively at multiple locations which form a hexagonal grid pattern that tiles the surface of the environment with remarkable geometric precision. Entorhinal grid cells send dense projections to hippocampal place cells, suggesting that grid cells may provide the elementary building blocks from which the hippocampus constructs spatial memory representations. The research proposed here will combine theoretical modeling studies with neurophysiological recording and lesion experiments in awake rats to investigate how grid cells generate their remarkable hexagonal firing fields, and how these firing fields can serve as a computational basis set for constructing hippocampal memory representations. This interdisciplinary research plan holds immense potential to revolutionize our understanding of cortico-hippocampal interactions, by revealing how the cortex packages incoming sensory information about the world into a form that can be utilized by the hippocampus for constructing coherent memory representations of familiar locations, objects, and events. Knowledge gained from these studies could usher a new era of discovery leading to novel therapies for reducing the burden of cognitive and memory deficits in patients suffering from psychiatric disorders.