Cerebral Protein Synthesis During Sleep and Memory Consolidation

本项目涉及的协议为09-M-0123、NCT00884702。 在2015财年融资期间，我们解决了以下问题： 与沃尔特里德陆军研究所(T Balkin)的同事合作，我们使用L-1-C-11亮氨酸PET方法测量了受试者在睡眠期间的RCP。为了解决睡眠恢复假说，我们测量了同一受试者在正常清醒、睡眠剥夺的清醒和睡眠中的RCP。我们假设RCP在睡眠期间增加，但在睡眠不足的清醒状态下，RCP保持在与休息清醒状态相当的水平。受试者在清醒、睡眠充足的状态下进行初始扫描。然后受试者在接下来的30小时内保持清醒，然后在睡眠不足但清醒的状态下接受第二次正电子发射计算机断层扫描。然后，受试者被鼓励在慢波睡眠期间接受第三次扫描时，在扫描仪中睡觉。受试者为年龄在18岁到28岁之间的健康男性和女性志愿者。我们排除了有神经和精神疾病病史、慢性疾病和睡眠障碍的受试者。我们的初步结果表明，在慢波睡眠期间，大脑某些区域的RCP有升高的趋势。 为了解决蛋白质合成在记忆巩固中的作用，我们正在确定睡眠依赖的RCP增加是否与睡眠依赖的记忆改善有关。我们使用纹理辨别任务(TDT)来评估学习和记忆。这项任务绩效的提高已被证明依赖于睡眠。TDT是特定于视网膜的，所以在一个半球进行训练(由于对侧视野的刺激)并不能提高另一个半球的表现。这使我们能够确定初级视觉皮质受过训练的半球中RCP的变化，并将未受训练的半球作为对照。这项任务在上午8点进行，受试者被随机分为午睡组(中午12：30-2点)或不午睡组，并在下午6点重新进行这项任务TDT的刺激总是在视野的下半部分，我们随机化受刺激的一侧(左或右)。下午12：30-2：00(无午睡或午睡机会)，受试者同时进行L-1-11亮氨酸正电子发射体层摄影和脑电检查。我们假设，在午睡期间花大量时间在慢波睡眠中的受试者，会观察到训练过的大脑半球RCP的增加。我们进一步假设，这一增长将与这项任务的两届政府之间业绩的改善有关。 所有受试者在第一次接受任务之前都是睡眠不足的。因此，我们计划并执行了一项仅限行为数据的初步研究。这项研究现已在《知觉和运动技能》杂志上发表。问题是，一晚的睡眠剥夺是否会抑制这项任务的编码。18名参与者被随机分配到睡眠剥夺或睡眠控制的条件下，在操作之后，被给予两次质地辨别任务。所有参与者都有90分钟的机会。两届政府之间的小憩。与编码前没有睡眠剥夺的参与者相比，编码前睡眠不足的参与者表现出类似的离线巩固。这些结果表明，在包括评估蛋白质合成在睡眠依赖记忆巩固中的作用的研究阶段，睡眠剥夺后的编码将是正常的。

The protocol involved in this project is 09-M-0123, NCT00884702. During the FY 2015 funding period, we addressed the following: In collaboration with our colleagues from the Walter Reed Army Institute of Research (T Balkin), we use the L-1-C-11leucine PET method to measure rCPS in human subjects during sleep. To address the restoration hypothesis of sleep, we measure rCPS in the same subject during normal wakefulness, sleep-deprived wakefulness, and sleep. We hypothesize that rCPS is increased during sleep, but that during sleep-deprived wakefulness, rCPS remain at levels comparable to rested wakefulness. Subjects undergo the initial scan in the awake, sleep-sated state. Subjects are then kept awake over the next 30 h and subsequently undergo a second PET scan in the sleep-deprived but awake state. Subjects are then encouraged to sleep in the scanner while they undergo a third scan during slow wave sleep. Subjects are healthy male and female volunteers between the ages of 18 and 28 y. We exclude subjects with a history of neurological and psychiatric disorders, chronic medical conditions, and sleep disorders. Our preliminary results indicate trends for elevated rCPS in some brain regions during slow wave sleep. To address the role of protein synthesis in memory consolidation, we are determining whether sleep-dependent increases in rCPS are associated with sleep-dependent improvements in memory. We use the Texture Discrimination Task (TDT) to assess learning and memory. Improvement on performance of this task has been demonstrated to depend on sleep. The TDT is retinotopically specific, so training in one hemisphere (due to stimuli in the contralateral visual field) does not improve performance in the opposite hemisphere. This allows us to determine changes in rCPS in the trained hemisphere of the primary visual cortex and use the untrained hemisphere as a control. The task is administered at 8 AM, subjects are randomized to nap (12:30-2 PM) or no-nap groups, and the task is re-administered at 6 PM. The stimulus of the TDT is always in the lower half of the visual field and we randomize the stimulated side (left or right). From 12:30-2 PM (no nap or nap opportunity), subjects undergo simultaneous L-1-11Cleucine PET and electroencephalography (EEG). We hypothesize that an increase in rCPS in the trained hemisphere will be observed in subjects who spent a significant time in slow wave sleep during the nap opportunity. We further hypothesize that this increase will correlate with the improvement in performance between the two administrations of the task. All subjects are sleep-deprived prior to the first administration of the task. Therefore, we planned and performed a behavioral data-only pilot study. This study is now in press in Perceptual and Motor Skills. The question was whether one night of sleep deprivation inhibits encoding on the task. Eighteen participants were randomized to a sleep deprivation or sleep control condition and, after the manipulation, were given two administrations of the texture discrimination task. All participants were given an opportunity for a 90 min. nap between the two administrations. Participants who were sleep deprived prior to encoding exhibited similar offline consolidation compared to participants who were not sleep deprived prior to encoding. These results indicate encoding will be normal following sleep deprivation in the phase of the study that involves assessing the role of protein synthesis in sleep-dependent memory consolidation.