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）：拟议的实验和仿真研究研究了睡眠期间记忆巩固的第一个可行机制之一。结果将阐明记忆过程中海马CA1区域的Schaffer抵押和颞肌输入的特定作用，以及在醒来和快速眼动（REM）睡眠期间NE和5-HT门如何和5-HT门。在REM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在几天内发生了变化。在最初新颖的环境中，有位置场的细胞从theta节奏峰附近的射击转变为在REM期间在Theta槽附近射击，同时保持其在清醒探索过程中的Theta峰活动。 REM期间的theta槽发射可能会唯一促进与现在熟悉的，皮层固定的记忆相关的海马内突触的电视，并允许学习新信息以及将新信息与旧记忆的整合。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5-羟色胺（5-HT）在theta相反转中，TA-CA1输入的增强，SC-CA1突触的降低和依赖Hippocampus的学习和依赖于Hippocampus的学习和依赖于Hippocampus。具体而言，提出了实验性和建模研究，以研究REM重新激活过程中NE和5-HT的缺失提供的假设提供了一个可以加强TA-CA1突触的环境，并且SC-CA1突触可能会减弱，从而表明REM睡眠在学习和记忆中具有独特的作用。了解睡眠期间记忆巩固的机制应导致针对学习障碍者和老年人的特定睡眠治疗。结果还将表明常规处方抗抑郁药的影响，例如选择性去甲肾上腺素能（SNRIS）和血清素能（SSRIS）再摄取抑制剂，对学习和记忆。