REM Sleep and Memory

快速眼动睡眠和记忆

基本信息

批准号：
7597014
负责人：
Gina R Poe
金额：
$ 33.06万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-03-01 至 2011-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): A number of confluent lines of evidence support a role for REM sleep in learning and memory consolidation. In the first grant period we showed changes in hippocampal neural activity during REM that correlate with experience and follow the course of memory consolidation (SA1), namely a reversal in phase of firing from theta rhythm peaks to troughs. We altered learning rates and performance strategies with REM deprivation (SA2) and enhancement (SA3) on a new behavioral task and measured the changes in the theta peak-to-trough reversal with these manipulations. Instead of manipulating REM sleep, this proposal seeks to determine the physiological events of REM sleep that are important for memory consolidation in a hippocampus-dependent task. We hypothesize that the absence of norepinephrine and serotonin during hippocampal sleep reactivation provides an environment wherein synapses in the direct entorhinal-to-CA1 path may be strengthened and CA3-to-CA1 synapses may be weakened (depotentiated). Depotentiation is theoretically necessary for clearing the temporary, modifiable associative memory network of the hippocampus to allow changes in the memory code with the arrival of new information. In Specific Aim 1 we will test the necessity of hippocampal reactivation during sleep for depotentiation and test the necessity of depotentiation for successful modification of memory in a switching task. By allowing sleep to occur normally while temporarily inactivating the hippocampus, we will isolate the contribution of hippocampal reactivation at fixed time points in the memory consolidation process. We expect that the mnemonic benefits of sleep will not be realized in hippocampal-dependent tasks when the hippocampus is inactivated before consolidation is complete. When we release sleep reactivation, we expect to see neural activity patterns in waking and in REM sleep that indicate the consolidation process had been arrested and the peak-to-trough theta phase reversal delayed. We also expect consolidation to continue normally from the point at which it had been stopped as shown by resumed improvement in behavioral performance. In Specific Aims 2 and 3 we will test the mnemonic necessity of the absence of the two neurotransmitter systems normally silent during REM sleep. We will allow REM sleep to occur, but introduce noradrenergic and serotoniergic agonists in the hippocampus during sleep, measuring the changes in learning and in the sleep/waking profile of cellular activity as in the first specific aim. These results should suggest mnemonic influences of different antidepressants which act with varying efficacy on the monoaminergic axis. In addition, this effort will contribute to the knowledge base of memory consolidation mechanisms to ultimately indicate effective ways to improve the memory and learning capabilities of impaired individuals.

描述（由申请人提供）：大量证据支持快速眼动睡眠在学习和记忆巩固中的作用。在第一个资助期，我们展示了 REM 期间海马神经活动的变化，这些变化与经验相关并遵循记忆巩固 (SA1) 的过程，即从 θ 节律峰值到波谷的放电阶段的逆转。我们在新的行为任务中通过快速眼动剥夺（SA2）和增强（SA3）来改变学习率和表现策略，并通过这些操作测量 theta 峰谷反转的变化。该提案旨在确定快速眼动睡眠的生理事件，而不是操纵快速眼动睡眠，这些生理事件对于海马依赖性任务中的记忆巩固非常重要。我们假设海马睡眠重新激活期间去甲肾上腺素和血清素的缺乏提供了一个环境，其中直接内嗅到 CA1 路径中的突触可能会增强，而 CA3 到 CA1 突触可能会减弱（弱化）。从理论上讲，去电位对于清除海马体的临时的、可修改的联想记忆网络是必要的，以允许随着新信息的到来而改变记忆代码。在具体目标 1 中，我们将测试睡眠期间海马重新激活以实现去潜能的必要性，并测试去潜能对切换任务中成功修改记忆的必要性。通过允许睡眠正常进行，同时暂时使海马体失活，我们将在记忆巩固过程中的固定时间点分离出海马体重新激活的贡献。我们预计，当海马体在巩固完成之前失活时，睡眠的助记益处将不会在海马依赖性任务中实现。当我们释放睡眠重新激活时，我们期望看到清醒和快速眼动睡眠中的神经活动模式，这表明巩固过程已经停止，峰谷 θ 相反转被延迟。我们还预计整合将从停止的点开始正常继续，正如行为表现恢复改善所表明的那样。在具体目标 2 和 3 中，我们将测试快速眼动睡眠期间通常保持沉默的两种神经递质系统缺失的助记必要性。我们将允许快速眼动睡眠发生，但在睡眠期间在海马体中引入去甲肾上腺素能和血清素能激动剂，测量学习和细胞活动的睡眠/觉醒特征的变化，如第一个具体目标中那样。这些结果应该表明不同抗抑郁药对记忆的影响，这些药物对单胺能轴具有不同的功效。此外，这项工作将有助于建立记忆巩固机制的知识库，最终指明提高受损个体记忆和学习能力的有效方法。