CRCNS: Path Intergration by the Grid Cell Network

CRCNS：网格单元网络的路径整合

• 批准号: 8196348
• 负责人: HUGH T BLAIR
• 金额: $ 31.58万
• 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 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196348
• 关键词: Agreement; Alcoholism; Alzheimer' s Disease; Amnesia; Anterior; Anxiety Disorders; Area; Award; Biological Neural Networks; Brain; Brain Diseases; Brain region; Cells; Cerebral cortex; Chronic; Code; Computer Simulation; Confusion; Dementia; Diagnosis; Disease; Disorientation; Dissociation; Dissociative Amnesias; Encephalitis; Endogenous depression; Epilepsy; Exhibits; Fimbria of hippocampus; Fire - disasters; Frequencies; Functional disorder; Future; Hippocampus (Brain); Human; Laws; Learning; Lewy Body Disease; Location; Maps; Measures; Memory; Memory impairment; Mental Depression; Mental disorders; Modeling; Movement; Multiple Sclerosis; Nerve Degeneration; Nervous system structure; Neurons; Parkinson Disease; Pathway interactions; Pattern; Perception; Phase; Plant Roots; Play; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Process; Property; Rattus; Reading; Recurrence; Research; Retrieval; Role; Schizophrenia; Signal Transduction; Sleep; Speed; Stress; Structure; Symptoms; Syndrome; Testing; Textiles; Thalamic structure; Theoretical model; Theta Rhythm; Time; Training; Visit; Work; base; central pattern generator; effective therapy; entorhinal cortex; insight; memory encoding; memory process; network models; neurophysiology; new therapeutic target; novel; postsynaptic; prevent; relating to nervous system; research study; simulation; theories

DESCRIPTION (provided by applicant): For as long as it has been possible to measure electrical activity in the nervous system, it has been known that the brain produces oscillatory rhythms. Some rhythms are generated during sleep, others during waking; certain patterns of oscillatory brain activity occur in all healthy people, while other patterns only occur in disease states such as epilepsy, clinical depression, or schizophrenia. Many different brain rhythms have been identified and characterized, and yet almost nothing is known about their function. We know that the brain oscillates, but we do not know why. Over the past few years, discoveries have been made that provide tantalizing new clues for answering this question, by suggesting that neural oscillations are very much like "threads" that the brain weaves together to create the "fabric" of memory and perception. In rats, one particular kind of oscillation referred to as "theta rhythm" is very predominant in the hippocampus and entorhinal cortex, brain areas that play a critical role in learning and memory. It is becoming increasingly clear that theta oscillations (in the frequency band of 4-12 Hz) are building blocks from which the hippocampus and entorhinal cortex can construct memory representations. The studies proposed here will combine neurophysiological recording experiments with computational modeling studies to investigate how the rat brain uses theta oscillations to form memories of familiar locations in space. Neurons called "place cells" and "grid cells" become active whenever a rat visits certain familiar locations, and these neurons are strongly synchronized by theta oscillations. Proposed computational modeling studies will investigate how place cells and grid cells use theta oscillations to encode spatial memories, and will seek to decipher the structure of the biological neural networks that perform this task. Proposed neurophysiology studies will attempt to show for the first time that neural oscillators in subcortical regions store memory representations using a "phase code," and will examine how the cerebral cortex interacts with subcortical oscillators to read out these memory representations. Pharmacological inactivation studies will be conducted to demonstrate how memory processing breaks down when neural oscillators are disrupted, which may help to explain the causes of memory impairment in humans who suffer from amnesic syndrome in conjunction with disorders like Alzheimer's disease, schizophrenia, depression, anxiety disorders, and post-traumatic stress. By elucidating how memories are formed from theta oscillations in spatial memory circuits, the research proposed here will provide groundbreaking new insights into the fundamental role that neural oscillations play in normal memory processes. This work may in the future make it possible to diagnose and treat brain diseases and mental disorders that currently are not well understood, but which may prove to have roots in dysfunction of the neural oscillators that provide the basic building blocks for memory and perception. PUBLIC HEALTH RELEVANCE: Degeneration of memory circuits in the hippocampus and entorhinal cortex can cause amnesia and dementia in a broad spectrum of neurodegenerative and psychiatric conditions, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, chronic alcoholism, multiple sclerosis, encephalitis, posttraumatic stress disorder, dissociative amnesia, and others. There are very few effective treatments for the memory impairment, confusion, disorientation, and dissociation from reality that can accompany these conditions. Research proposed here will help to identify new therapeutic targets for treating these symptoms by demonstrating how oscillatory neural networks in the hippocampus, entorhinal cortex, and associated brain regions of rats are involved in regulating memory storage and retrieval.

描述（由申请人提供）：自从可以测量神经系统中的电活动以来，就已知大脑会产生振荡节律。有些节律是在睡眠期间产生的，另一些则是在清醒时产生的。某些振荡大脑活动模式发生在所有健康人身上，而其他模式仅发生在癫痫、临床抑郁症或精神分裂症等疾病状态下。许多不同的大脑节律已被识别和表征，但对其功能几乎一无所知。我们知道大脑会振荡，但我们不知道为什么。在过去的几年里，一些发现为回答这个问题提供了诱人的新线索，它们表明神经振荡非常像大脑编织在一起形成记忆和感知“结构”的“线”。在大鼠中，一种被称为“θ节律”的特殊振荡在海马体和内嗅皮层中非常重要，这些大脑区域在学习和记忆中发挥着关键作用。越来越清楚的是，θ 振荡（4-12 Hz 频段）是海马体和内嗅皮层构建记忆表征的基石。这里提出的研究将神经生理学记录实验与计算模型研究结合起来，研究大鼠大脑如何利用θ振荡形成对空间中熟悉位置的记忆。每当老鼠访问某些熟悉的位置时，称为“位置细胞”和“网格细胞”的神经元就会变得活跃，并且这些神经元通过 θ 振荡强烈同步。拟议的计算模型研究将研究位置细胞和网格细胞如何使用 theta 振荡来编码空间记忆，并将寻求破译执行此任务的生物神经网络的结构。拟议的神经生理学研究将尝试首次证明皮质下区域的神经振荡器使用“相位代码”存储记忆表征，并将检查大脑皮层如何与皮质下振荡器相互作用以读出这些记忆表征。将进行药理学失活研究，以证明当神经振荡器被破坏时，记忆处理如何被破坏，这可能有助于解释患有健忘症以及阿尔茨海默病、精神分裂症、抑郁症、焦虑症等疾病的人类记忆障碍的原因和创伤后应激障碍。通过阐明空间记忆回路中的θ振荡如何形成记忆，本文提出的研究将为神经振荡在正常记忆过程中所发挥的基本作用提供突破性的新见解。这项工作将来可能使诊断和治疗目前尚不清楚的脑部疾病和精神障碍成为可能，但事实可能证明这些疾病的根源在于神经振荡器的功能障碍，而神经振荡器是记忆和感知的基本组成部分。 公共健康相关性：海马和内嗅皮层记忆回路的退化可导致多种神经退行性和精神疾病的失忆和痴呆，包括阿尔茨海默病、帕金森病、路易体痴呆、慢性酒精中毒、多发性硬化症、脑炎、创伤后应激障碍障碍、解离性遗忘症等。对于伴随这些病症而来的记忆障碍、混乱、迷失方向和脱离现实，有效的治疗方法很少。本文提出的研究将通过证明大鼠海马体、内嗅皮层和相关大脑区域的振荡神经网络如何参与调节记忆存储和检索，帮助确定治疗这些症状的新治疗靶点。