REM Sleep and Memory

描述（由申请人提供）：我们假设在REM睡眠期间前脑中NE的缺乏和向REM睡眠（TR）的纺锤体丰富过渡允许突触去增强，其是新记忆正常同化到全局记忆网络图式中的基础。创伤后应激障碍是一种与异常高的去甲肾上腺素张力、强烈的做梦和侵入性记忆有关的疾病。我们假设，在睡眠中去甲肾上腺素（NE）的异常存在，阻止了正常的记忆巩固的重要去增强过程，从而防止新的记忆与熟悉的记忆整合在新皮层记忆网络。我们将同时记录海马和LC，以确定在无NE的情况下（即在纺锤体产生期间），非REM睡眠期间海马的再激活是否以不同的方式发生。我们将检查海马再激活事件的变化指示可塑性，如突发尖峰衰减变化，因果熵和功能聚类。我们将研究与局部电场电位相关的尖峰放电模式，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期间看到的新记忆不同地被激活，而且这种重放在非快速眼动睡眠纺锤波期间将是相位特异性的，就像它们在快速眼动睡眠中是相位特异性的一样。我们假设，LC沉默是必要的，以产生纺锤体摆在首位，以及突触的加强和削弱的影响纺锤体相位相关的射击。为了测试NE不存在的必要性，我们将在睡眠期间在亚觉醒水平（~3 Hz）刺激LC，无论何时我们看到皮层或海马中的纺锤波直到下一次觉醒。我们预计，产生的纺锤波数量会显著减少，海马体在非快速眼动睡眠中重放产生的去增强作用会消失，记忆巩固会受损，尤其是在逆转任务中。这项研究将对开发有效的策略有很大的影响，这些策略可以选择性地降低在睡眠的做梦和纺锤体阶段重新激活的突触网络，过度强烈的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.