Understanding memory consolidation by studying pharmacologically enhanced naps

通过研究药理学增强小睡来了解记忆巩固

• 批准号: 7486204
• 负责人: SARA CAROLE MEDNICK
• 金额: $ 15.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7486204
• 关键词: Behavioral; Cerebrum; Condition; Development; Dose; Educational process of instructing; Electroencephalography; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Intervention; Investigation; Knowledge; Lead; Learning; Literature; Measures; Mechanics; Memory; Memory impairment; Mentors; Methods; Motor; Napping; Patients; Perceptual learning; Performance; Pharmaceutical Preparations; Pharmacology; Placebos; Play; Population; Process; Psychiatric therapeutic procedure; Psychopharmacology; REM Sleep; Relative (related person); Research; Research Proposals; Research Training; Role; Sleep; Sleep Stages; Stage II Sleep; Stage III Sleep; Staging; Statistical Methods; Training; Training Support; Work; base; career; density; design; dosage; improved; memory process; neurobiological mechanism; relating to nervous system; response; zolpidem

DESCRIPTION (provided by applicant): The primary goal of this mentored project is to prepare the candidate for a career in the investigation of the pharmacological basis of sleep-dependent memory consolidation. The training plan include: 1) gaining broad knowledge in psychopharmacology, including experimental and statistical methods for conducting pharmacology studies; 2) career development, and 3) teaching. The research plan aims to examine the mechanics of specific sleep parameters in enhancing select memory processes by pharmacologically modifying these sleep parameters during daytime sleep, or naps. Previous studies have shown that 1) a wide variety of memory improvement requires post-training nocturnal sleep, 2) these improvements have been correlated with specific sleep stages, and 3) the same memory improvements occur during naps. Further, studies suggest the neuromodulatory fluctuations related to specific sleep stages influence memory processing. New pharmacological agents, gaboxadol and zolpidem, have been shown to selectively increase specific sleep stages in nocturnal sleep. The first aim of this research is to determine the doses of gaboxadol and zolpidem that will enhance specific sleep stages in a nap. We will then apply our established methods of studying sleep-stage-specific learning in the nap to investigate whether pharmacologically enhanced naps will improve memory consolidation over non enhanced naps. We will measure these differences behaviorally, with EEG, and with functional magnetic resonance imaging (fMRI). The research proposal identifies three main thrusts to support the training plan: (1) design and implement a dose-dependent study examining the effect of pharmacological agents on sleep stages during a nap, (2) identify and analyze the relationship between dose-dependent changes in sleep stages and in drug dosage, and (3) correlate behavioral and cerebral responses to specific memory tasks produced by pharmacological intervention. These studies will lead to better understanding of the neuromodulatory mechanisms during sleep (naps) that play a role in memory consolidation processes. The research and training will form the foundation for future work in the neurobiological mechanisms underlying memory consolidation. These studies have implications for treatment of psychiatric patients and other populations with memory impairment through improved pharmacological interventions that manipulate sleep as a means of improving memory performance.

描述（由申请人提供）：这个指导项目的主要目标是准备候选人的职业生涯中的睡眠依赖性记忆巩固的药理学基础的调查。培训计划包括：1）获得广泛的精神药理学知识，包括进行药理学研究的实验和统计方法; 2）职业发展; 3）教学。该研究计划旨在通过在白天睡眠或午睡期间对这些睡眠参数进行连续修改来检查特定睡眠参数在增强选择记忆过程中的机制。以前的研究表明：1）各种各样的记忆改善需要训练后的夜间睡眠，2）这些改善与特定的睡眠阶段相关，3）午睡期间也会出现同样的记忆改善。此外，研究表明，与特定睡眠阶段相关的神经调节波动会影响记忆处理。新的药理学药物加波沙朵和唑吡坦已被证明可以选择性地增加夜间睡眠中的特定睡眠阶段。这项研究的第一个目的是确定加波沙朵和唑吡坦的剂量，这将增强午睡中的特定睡眠阶段。然后，我们将应用我们已经建立的研究午睡中睡眠阶段特定学习的方法，来研究强化午睡是否会比非强化午睡改善记忆巩固。我们将通过行为学、脑电图和功能性磁共振成像（fMRI）来测量这些差异。该研究计划确定了三个主要目标来支持训练计划：（1）设计并实施一项剂量依赖性研究，检查药物对午睡期间睡眠阶段的影响，（2）确定并分析睡眠阶段和药物剂量的剂量依赖性变化之间的关系，以及（3）将行为和大脑反应与药物干预产生的特定记忆任务相关联。这些研究将导致更好地了解睡眠（午睡）期间的神经调节机制，在记忆巩固过程中发挥作用。这项研究和培训将为未来记忆巩固的神经生物学机制奠定基础。这些研究对精神病患者和其他记忆障碍人群的治疗具有重要意义，这些患者可以通过改善药物干预来控制睡眠，从而改善记忆表现。