Brain Rhythms and Episodic Memory Processes

描述（由申请人提供）：遗忘综合征和与年龄相关的认知能力下降目前发病率很高，但有效的治疗方法很少。这项提议的长期目标是表征与衰老相关的认知能力下降的神经生物学基础，并制定治疗这种下降的治疗策略。这些目标与NIH支持创新研究、延长健康寿命、减少疾病和残疾负担的使命相吻合。该项目将利用健忘症和认知衰老的大鼠模型，研究与情景记忆编码相关的脑节律相互作用的基本机制。具体目的是测试一种新的策略来提高记忆表现，并评估潜在的情景记忆编码机制。在正常的大鼠中，破坏中隔功能会损害记忆表现，相反，电刺激中隔会改善记忆表现。通过同时记录海马脑电图，刺激穹窿，并在径向臂水迷宫（RAWM）中跟踪行为，我们将直接评估不同电刺激模式的生理和行为后果。具体目的是改善内侧间隔失活导致的遗忘大鼠的记忆，以及改善自然发生空间缺陷的老年大鼠的记忆。我们将测试theta（4-10赫兹）和gamma（30-50赫兹）频率之间的连贯活动对记忆编码或检索至关重要的假设。我们预测theta-gamma相干性将预测记忆表现，并且增加这种相干性的刺激模式将同时增强记忆机制。本实验的结果将阐明内源性同步节律对记忆的影响，并可能导致改善人类记忆的治疗干预。尽管没有阿尔茨海默病或其他疾病，但认知能力下降和记忆障碍往往发生在老年时期。这个项目测试了一种方法，在患有失忆症的年轻大鼠和患有自然记忆障碍的老年大鼠的大脑中使用电刺激来修复学习缺陷。随着美国65岁及以上人口在未来十年的增加，这种治疗将成为我们老龄化社会的一个更加迫切的需求。

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.