CRCNS: Path Integration by the Grid Cell Network

CRCNS：网格单元网络的路径集成

• 批准号: 7216448
• 负责人: HUGH T BLAIR
• 金额: $ 36.49万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7216448
• 关键词: behavior test; central neural pathway /tract; computational neuroscience; developmental neurobiology; electrical property; experimental brain lesion; hippocampus; laboratory rat; memory; model design /development; neuroanatomy; neurons; neurophysiology; space perception; voltage /patch clamp

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.

描述（由申请人提供）：海马体中的记忆回路对于储存和检索我们生活经历的信息至关重要，使我们能够对我们周围的世界建立准确的表征——这是正常认知和行为的基本要求。海马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。为了更好地治疗这些疾病，有必要了解海马体中支持学习和记忆的细胞计算。侵入性的神经生理学实验不能在人类身上进行，所以很多关于细胞记忆机制的已知知识都是从动物模型，尤其是啮齿动物身上学来的。啮齿类动物非常擅长学习在熟悉的区域导航，这些能力依赖于大脑海马和海马旁区域的空间记忆回路（就像人类一样）。啮齿类动物的海马体中含有一种叫做“位置细胞”的神经元，当动物访问特定位置时，这些神经元会选择性地放电，为熟悉的空间环境的记忆表征编码提供神经基质。然而，目前尚不清楚来自海马体外部的信号是如何被位置细胞处理以编码空间记忆的。最近，人们发现大鼠的内嗅皮层含有一种以前不为人知的神经元群，叫做“网格细胞”。当老鼠在空间环境中导航时，网格细胞有选择地在多个位置发射，形成一个六边形网格图案，以惊人的几何精度铺满环境表面。内嗅网格细胞向海马体位置细胞发送密集的投影，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建块。本研究将理论建模研究与清醒大鼠的神经生理记录和损伤实验相结合，探讨网格细胞如何产生显著的六边形放电场，以及这些放电场如何作为构建海马记忆表征的计算基础集。这个跨学科的研究计划具有巨大的潜力，通过揭示皮层如何将关于世界的感官信息打包成一种形式，海马体可以利用这种形式来构建对熟悉的地点、物体和事件的连贯记忆表征，从而彻底改变我们对皮质-海马体相互作用的理解。从这些研究中获得的知识可能会开启一个新的发现时代，导致新的治疗方法，以减轻精神疾病患者的认知和记忆缺陷的负担。