Brain Rhythms and Episodic Memory Processes

描述(由申请人提供)：遗忘症和年龄相关的认知能力下降表现出显著的发病率，但几乎没有有效的治疗方法。这项建议的长期目标是描述与衰老相关的认知衰退的神经生物学基础，并开发治疗这种衰退的治疗策略。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。该项目将使用健忘症和认知老化的大鼠模型，研究与情景记忆编码相关的大脑节奏相互作用的基本机制。这些特定的目标将测试一种新的提高记忆性能的策略，并评估潜在的情景记忆编码机制。在正常大鼠中，记忆表现因破坏内侧隔膜功能而受损，反之，通过电刺激隔膜而改善。通过同时记录海马脑电、刺激穹隆和在放射臂水迷宫(RAWM)中跟踪行为，我们将直接评估不同模式的电刺激的生理和行为后果。其具体目的是改善因内侧隔失活而被遗忘的大鼠的记忆，并改善自然发生空间缺陷的老年大鼠的记忆。我们将检验这一假设，即theta(4-10赫兹)和伽马(30-50赫兹)频率之间的相干活动对记忆编码或提取至关重要。我们预测，theta-Gamma一致性将预测记忆性能，并且增加这种一致性的刺激模式将伴随着增强记忆机制。这些实验的结果将阐明内源性同步节律性对记忆的影响，并可能导致改善人们记忆的治疗干预。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期间。这个项目测试了一种方法，通过大脑中的电刺激来修复患有健忘症的年轻大鼠和患有自然记忆障碍的老年大鼠的学习缺陷。随着未来十年美国65岁及以上人口的增加，在我们老龄化的社会，这样的治疗将成为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.