REM Sleep and Memory

描述(由申请人提供)：我们假设，在REM睡眠期间，前脑中没有NE，以及向REM睡眠的纺锤体丰富的过渡(TR)允许突触去增强，这是正常将新记忆同化到全局记忆网络模式的基础。创伤后应激障碍是一种与异常高的去甲肾上腺素、强烈的梦境和侵入性记忆有关的疾病。我们假设，睡眠中去甲肾上腺素(NE)的异常存在阻止了正常记忆巩固的重要去增强过程，从而阻止了新记忆与新皮质记忆网络中熟悉记忆的整合。我们将同时从海马和LC进行记录，以确定在没有NE的情况下(即在纺锤体产生期间)，在非REM睡眠期间，海马的重新激活是否会发生不同的情况。我们将研究海马区的重新激活事件，以寻找指示可塑性的变化，如爆发峰波衰减变化，因果熵和功能聚集。我们将研究与局部电场电位有关的尖峰放电模式，并期待看到熟悉的、已经巩固的记忆被激活的方式与我们在REM睡眠中看到的新记忆不同，并且这种重放将在非REM睡眠纺锤波中是特定于阶段的，就像它们是REM睡眠中的theta特定的阶段一样。我们假设LC沉默是产生纺锤波所必需的，也是纺锤体相关联放电的突触增强和减弱效应所必需的。为了测试NE缺席的必要性，我们将在睡眠期间以亚唤醒水平(~3赫兹)刺激LC，无论何时我们看到大脑皮层或海马体中的纺锤波，直到下一次醒来。我们预计产生的纺锤波数量会显著减少，在非快速眼动睡眠中海马体重放产生的去增强作用会丧失，记忆巩固会受到损害，特别是在颠倒任务中。这项研究将对开发有选择地缩小突触网络规模的有效策略具有重要意义，这些突触网络在睡眠的做梦和纺锤阶段重新激活，对那些无法正常化和整合创伤记忆的人来说，对这些突触网络的过度强烈保留会削弱他们的能力。

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.