CRCNS - Neuromodulation of Hippocampal Synaptic Plasticity in Waking & REM Sleep

CRCNS - 清醒时海马突触可塑性的神经调节

• 批准号: 7113222
• 负责人: Gina R Poe
• 金额: $ 23.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113222
• 关键词: REM sleep; action potentials; brain electrical activity; computer data analysis; computer simulation; electrical conductance; hippocampus; laboratory rat; learning; long term potentiation; male; memory; neural information processing; neural plasticity; neural transmission; neurotransmitter agonist; neurotransmitter metabolism; neurotransmitter transport; norepinephrine; potassium ion; serotonin; single cell analysis; synapses; wakefulness

DESCRIPTION (provided by applicant): The proposed experiments and simulation studies investigate one of the first feasible mechanisms for memory consolidation during sleep. The results will elucidate particular roles for the Schaffer Collateral and temporo-ammonic inputs to the hippocampal CA1 region in memory processing and how NE and 5-HT gate these pathways during waking and Rapid Eye Movement (REM) sleep. During REM sleep, we have found that reactivation of hippocampal cells changes over the course of several days as the animals became familiar with an environment. Cells with place fields in an initially novel environment switch from firing near the theta rhythm peaks to firing near the theta troughs during REM, while maintaining their theta peak activity during waking exploration. Theta trough firing during REM may uniquely facilitate depotentiation of intra-hippocampal synapses which are associated with now familiar, cortically-consolidated memories and allow for learning of new information and the integration of novel information with old memories. This proposal seeks to test the role of the uniquely REM-suppressed neurotransmitters norepinephrine (NE) and serotonin (5-HT) in theta phase reversal, potentiation of TA-CA1 inputs, depotentiation of SC-CA1 synapses and hippocampus-dependent learning and memory. Specifically, experimental and modeling studies are proposed to investigate the hypothesis that the absence of NE and 5-HT during REM reactivation provides an environment wherein TA-CA1 synapses may be strengthened and SC-CA1 synapses may be weakened, thus indicating a unique role for REM sleep in learning and memory. Understanding the mechanisms underlying memory consolidation during sleep should lead to sleep-specific treatments for learning disabled persons and the elderly. The results will also indicate effects of commonly prescribed anti-depressants, such as selective noradrenergic (SNRIs) and serotonergic (SSRIs) re-uptake inhibitors, on learning and memory.

描述（由申请人提供）：所提出的实验和模拟研究调查了睡眠期间记忆巩固的第一个可行机制。结果将阐明海马 CA1 区的谢弗侧支和颞氨输入在记忆处理中的特殊作用，以及 NE 和 5-HT 在清醒和快速眼动 (REM) 睡眠期间如何控制这些通路。在快速眼动睡眠期间，我们发现，随着动物熟悉环境，海马细胞的重新激活会在几天内发生变化。在快速眼动期间，在最初的新环境中具有位置场的细胞从θ节律峰值附近的放电切换到θ波谷附近的放电，同时在清醒探索期间保持其θ峰值活动。快速眼动期间的 Theta 波谷放电可能独特地促进海马内突触的去电位，这些突触与现在熟悉的皮质巩固记忆相关，并允许学习新信息以及将新信息与旧记忆整合。该提案旨在测试独特的 REM 抑制神经递质去甲肾上腺素 (NE) 和血清素 (5-HT) 在 θ 相反转、TA-CA1 输入增强、SC-CA1 突触减弱以及海马依赖性学习和记忆中的作用。具体来说，实验和模型研究旨在调查这样的假设：在 REM 重新激活过程中 NE 和 5-HT 的缺失提供了一个环境，其中 TA-CA1 突触可能被加强，而 SC-CA1 突触可能被削弱，从而表明 NE 和 5-HT 的独特作用快速眼动睡眠有助于学习和记忆。了解睡眠期间记忆巩固的机制应该可以为学习障碍者和老年人提供针对睡眠的治疗方法。结果还将表明常用抗抑郁药，例如选择性去甲肾上腺素能（SNRI）和血清素能（SSRI）再摄取抑制剂对学习和记忆的影响。