Brain Rhythms and Episodic Memory Processes

大脑节律和情景记忆过程

基本信息

批准号：
8127731
负责人：
Prasad Shirvalkar
金额：
$ 3.72万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-25 至 2012-05-24
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8127731
关键词：
Affect Age Age-associated memory impairment Aging Alzheimer&apos s Disease Amnesia Amnestic Disorder Animals Behavior Behavioral Biological Preservation Brain Brain region Code Cognitive Cognitive aging Cognitive deficits Control Animal Custom Data Elderly Electric Stimulation Electrical Stimulation of the Brain Electroencephalography Episodic memory Failure Frequencies Functional disorder Goals Hippocampus (Brain)Impaired cognition Individual Lead Learning Life Link Measures Medial Memory Memory impairment Mission Modeling Morbidity - disease rate Morphology Muscimol Neurobiology Neurocognitive Neurons Pattern Performance Periodicity Physiological Play Population Procedures Process Property Protocols documentation Pyramidal Cells Radial Rattus Relative (related person)Research Role Societies Structure Synapses Synaptic plasticity Testing Therapeutic Therapeutic Intervention Theta Rhythm United States National Institutes of Health Water Work age related aged arm behavior measurement burden of illness density design disability effective therapy improved information processing innovation memory encoding memory process memory retrieval neuron loss neuroregulation normal aging novel strategies repaired research study

项目摘要

DESCRIPTION (provided by applicant): Amnestic syndromes and age-associated cognitive decline present significant morbidity, yet have few effective treatments. The long-term goals of this proposal are to characterize the neurobiological substrates of cognitive decline associated with aging and to develop therapeutic strategies to treat such decline. These goals dovetail with the NIH mission to support innovative research, extend healthy life and reduce the burdens of illness and disability The project will study fundamental mechanisms of brain rhythm interactions relevant to episodic memory coding using a rat model of amnesia and cognitive aging. The specific aims will test a novel strategy to improve memory performance, and evaluate potential episodic memory encoding mechanisms. In normal rats, memory performance is impaired by disrupting medial septal function, and conversely, improved by electrical stimulation of the septum. By simultaneously recording hippocampal EEG, stimulating the fornix, and tracking behavior in a Radial Arm Water Maze (RAWM), we will directly evaluate the physiological and behavioral consequences of different patterns of electrical stimulation. The specific aims are to ameliorate memory in rats made amnestic by medial septal inactivation, and to improve memory in aged rats who have naturally occurring spatial deficits. We will test the hypothesis that coherent activity between theta (4-10 Hz) and gamma (30-50 Hz) frequencies are crucial for memory encoding or retrieval. We predict that theta-gamma coherence will predict memory performance, and that stimulation patterns that increase such coherence will concomitantly enhance memory mechanisms. The results of the proposed experiments will elucidate the influence of endogenous synchronous rhythmicity in memory, and may lead to therapeutic interventions for improving memory in people. Cognitive decline and memory impairments often occur during old age, despite the absence of Alzheimer's disease or other illness. This project tests an approach to repair learning deficits in both young rats with amnesia and old rats with natural memory impairments using electrical stimulation in the brain. As the population of the US aged 65 and over increases over the next decade, such treatments will become a more urgent need in our aging society.

描述（由申请人提供）：炎症综合征和与年龄相关的认知下降具有明显的发病率，但几乎没有有效的治疗方法。该提案的长期目标是表征与衰老相关的认知下降的神经生物学基质，并制定治疗这种下降的治疗策略。这些目标与NIH的任务相吻合，旨在支持创新研究，延长健康的生命并减轻疾病和残疾的负担。具体目的将测试一种新的策略，以改善记忆性能，并评估潜在的情节记忆编码机制。在正常的大鼠中，记忆性能通过破坏内侧间隔功能而受到损害，相反，通过隔膜的电刺激来改善。通过同时记录海马脑电图，刺激前伤并跟踪径向臂水迷宫（RAWM）中的行为，我们将直接评估电刺激的不同模式的生理和行为后果。具体的目的是改善通过内侧灭活的大鼠使记忆力减轻，并改善自然存在空间缺陷的老年大鼠的记忆。我们将检验以下假设：Theta（4-10 Hz）和伽马（30-50 Hz）之间的相干活性对于记忆编码或检索至关重要。我们预测，theta-gamma的连贯性将预测记忆性能，并且增加这种连贯性的刺激模式将同时增强记忆机制。提出的实验的结果将阐明内源性同步节奏在记忆中的影响，并可能导致治疗干预措施以改善人们的记忆力。尽管没有阿尔茨海默氏病或其他疾病，但认知能力下降和记忆力障碍通常会在老年内发生。该项目测试了一种修复患有失忆症的年轻大鼠和老鼠，自然记忆障碍的方法，使用大脑中的电刺激。随着美国65岁及65岁的人口在接下来的十年中的增长，这种治疗将成为我们老龄化社会的迫切需求。