REM Sleep and Memory

描述（由申请人提供）：我们假设，在快速眼动睡眠期间，前脑内NE的缺失以及向快速眼动睡眠（TR）的纺锤波丰富过渡允许突触去增强，这是新记忆正常同化到全局记忆网络图式的基础。创伤后应激障碍是一种与异常高的去甲肾上腺素能张力、强烈的梦境和侵入性记忆有关的疾病。我们假设，在睡眠期间，去甲肾上腺素（NE）的异常存在阻止了正常记忆巩固的重要去增强过程，从而阻止了新皮层记忆网络中新记忆与熟悉记忆的整合。我们将同时记录海马体和LC的数据，以确定在没有NE的非快速眼动睡眠期间（即纺锤体产生期间）海马体的再激活是否会发生不同。我们将检查海马体再激活事件的变化表明可塑性，如脉冲峰衰减变化，因果熵和功能聚类。我们将研究与局部电场电位相关的尖波放电模式，并期望看到熟悉的、已经巩固的记忆与我们在快速眼动睡眠中看到的新记忆的激活方式不同，并且这种重放将在非快速眼动睡眠中具有特定的阶段，就像它们在快速眼动睡眠中具有特定的阶段一样。我们假设LC沉默首先是产生纺锤波以及纺锤波相相关放电的突触增强和减弱效应所必需的。为了测试NE缺失的必要性，我们将在睡眠期间以亚唤醒水平（~ 3hz）刺激LC，每当我们看到皮层或海马体中的纺锤波时，直到下一次醒来。我们预计纺锤波产生的数量会显著减少，海马在非快速眼动睡眠中重播产生的失能现象会消失，记忆巩固也会受损，尤其是在逆向任务中。这项研究将对开发有效的策略来选择性地减少在睡眠的做梦和纺锤波阶段重新激活的突触网络具有重要意义，这些突触网络的过度保留会使那些无法正常化和整合创伤记忆的人变得虚弱。

DESCRIPTION (provided by applicant): We hypothesize that the absence of NE in the forebrain during REM sleep and the spindle-rich transition to REM sleep (TR) allows for synaptic depotentiation underlying normal assimilation of new memories into the global memory network schema. Post-traumatic stress disorder is one condition associated with abnormally high noradrenergic tone, intense dreaming and intrusive memories. We hypothesize that an abnormal presence of norepinephrine (NE) during sleep prevents the important depotentiation process of normal memory consolidation and thus prevents novel memories from being integrated with familiar memories in the neocortical memory network. We will record from the hippocampus and LC simultaneously to determine whether hippocampal reactivation during non-REM sleep occurs differently in the absence of NE (i.e. during spindle production). We will examine hippocampal reactivation events for changes indicative of plasticity, like burst spike attenuation changes, Causal Entropy and Functional Clustering. We will examine spike firing patterns in relation to local electrical field potentials and expect to see familiar, already consolidated memories activated differently than novel memories as we have seen during REM sleep, and that such replay will be phase specific during non-REM sleep spindles just as they are phase specific to theta in REM sleep. We hypothesize that LC silence is necessary to generate spindles in the first place as well as for the synaptic strengthening and weakening effects of spindle-phase associated firing. To test the necessity for NE to be absent we will stimulate the LC at sub-arousal levels (~3 Hz) during sleep whenever we see spindles in the cortex or hippocampus through to the next awakening. We expect a marked reduction in the number of spindles generated, a loss of the depotentiation that hippocampal replay in non-REM sleep produces, and impaired memory consolidation especially for reversal tasks. This research will have strong implications for the development of effective strategies to selectively downscale synaptic networks reactivated during the dreaming and spindle stages of sleep the overly strong retention of which is debilitating in those unable to normalize and integrate their traumatic memories.