REM Sleep and Memory

快速眼动睡眠和记忆

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7597014
• 关键词: Adrenergic beta-Antagonists; Affect; Agonist; Animals; Antidepressive Agents; Behavioral; Brain; Cells; Chemosensitization; Code; Distal; Drug usage; Environment; Event; Grant; Hippocampus (Brain); Homosynaptic Depression; Hour; Individual; Infusion procedures; Learning; Literature; Measures; Memory; Memory impairment; Mental disorders; Modification; Neurons; Neurotransmitters; Norepinephrine; Patients; Pattern; Performance; Phase; Physiological; Process; REM Sleep; Research; Research Personnel; Research Proposals; Reversal Learning; Role; Selective Serotonin Reuptake Inhibitor; Serotonin; Serotonin Agents; Sleep; Synapses; System; Testing; Theta Rhythm; Time; Training; depressed; deprivation; experience; flexibility; improved; knowledge base; noradrenergic; novel; prevent; programs; receptor; relating to nervous system; response

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）：许多汇合的证据线支持REM睡眠在学习和记忆巩固中的作用。在第一个赠款期间，我们显示了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过程（SA1），即从Theta Rhythm Peaks触发到槽的阶段逆转。我们在新的行为任务上改变了学习率和绩效策略（SA2）和增强（SA3），并通过这些操纵来衡量Theta峰值到潮流逆转的变化。该建议没有操纵REM睡眠，而是试图确定REM睡眠的生理事件，这对于海马依赖性任务中的记忆巩固很重要。我们假设在海马睡眠重新激活过程中缺乏去甲肾上腺素和5-羟色胺为环境提供了一个环境，在这种环境中，直接内hin骨到CA1路径中的突触可以得到加强，并且可以削弱CA3-to-CA1突触（驱逐）。从理论上讲，量化对于清除海马的临时，可修改的关联内存网络是必需的，以便随着新信息的到来允许内存代码的更改。在特定的目标1中，我们将测试睡眠期间海马重新激活的必要性，以进行屈服，并测试在切换任务中成功修改内存的台性必要性。通过允许睡眠正常发生在暂时灭活海马时，我们将隔离记忆巩固过程中固定时间点的海马重新激活的贡献。我们预计，当海马在巩固完成之前，在海马依赖性任务中不会实现睡眠的助攻益处。当我们释放睡眠重新激活时，我们期望在醒来和REM睡眠中看到神经活动模式，表明巩固过程已被逮捕，并且峰值theta相位逆转延迟。我们还期望从停止行为表现的改善所表明的那样，从停止的地步开始正常巩固。在特定的目标2和3中，我们将测试通常在REM睡眠期间通常保持沉默的两个神经递质系统的助记符必要性。我们将允许REM睡眠发生，但是在睡眠期间，在海马中引入去甲肾上腺素能和血清素激动剂，测量学习的变化以及细胞活动的睡眠/清醒曲线，如第一个特定目的。这些结果应表明不同抗抑郁药对单胺能轴的作用的助记素影响。此外，这项努力将有助于记忆巩固机制的知识基础，以最终指出改善受损个人的记忆和学习能力的有效方法。