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(申请人提供)：自从有可能测量神经系统中的电活动以来，就已经知道大脑产生振荡节律。有些节律是在睡眠中产生的，另一些是在清醒时产生的；某些模式的振荡大脑活动在所有健康人中都会发生，而其他模式只在疾病状态下才会发生，如癫痫、临床抑郁症或精神分裂症。许多不同的大脑节律已经被识别和表征，但对它们的功能几乎一无所知。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，已经有一些发现为回答这个问题提供了诱人的新线索，这些发现表明，神经振荡很像是大脑编织在一起的“线”，创造了记忆和感知的“织物”。在大鼠的海马体和内嗅觉皮质中，一种特殊的振荡被称为“theta节律”，这两个脑区在学习和记忆中起着关键作用。越来越清楚的是，theta振荡(在4-12赫兹的频段内)是海马体和内嗅觉皮质构建记忆表征的基础。这里提出的研究将结合神经生理学记录实验和计算建模研究，以调查大鼠大脑如何利用theta振荡来形成对空间中熟悉位置的记忆。当一只大鼠访问某些熟悉的位置时，被称为“位置细胞”和“网格细胞”的神经元就会变得活跃，而这些神经元是由theta振荡强烈同步的。拟议的计算建模研究将调查位置细胞和网格细胞如何使用theta振荡来编码空间记忆，并将寻求破译执行这一任务的生物神经网络结构。拟议的神经生理学研究将首次试图表明，皮质下区域的神经振荡器使用“相码”存储记忆表征，并将研究大脑皮层如何与皮质下振荡器相互作用来读出这些记忆表征。将进行药理学失活研究，以证明当神经振荡器被扰乱时，记忆处理是如何崩溃的，这可能有助于解释患有失忆综合征并伴有阿尔茨海默病、精神分裂症、抑郁症、焦虑症和创伤后应激等疾病的人类记忆障碍的原因。通过阐明空间记忆电路中的theta振荡是如何形成记忆的，这里提出的这项研究将为神经振荡在正常记忆过程中扮演的基本角色提供开创性的新见解。这项工作未来可能使诊断和治疗大脑疾病和精神障碍成为可能，这些疾病和精神障碍目前还没有被很好地了解，但可能被证明是神经振荡器功能障碍的根源，神经振荡器为记忆和感知提供基本的构件。 公共卫生相关性：海马体和内嗅觉皮质记忆回路的退化可在多种神经退行性疾病和精神疾病中导致健忘症和痴呆症，包括阿尔茨海默病、帕金森氏病、路易体痴呆症、慢性酒精中毒、多发性硬化症、脑炎、创伤后应激障碍、分离性健忘症等。很少有有效的治疗方法来治疗伴随这些情况而来的记忆障碍、困惑、定向障碍和与现实脱节。这里提出的研究将有助于通过展示大鼠海马体、内嗅觉皮质和相关脑区的振荡神经网络如何参与调节记忆存储和提取，来确定治疗这些症状的新治疗靶点。