Cerebral Protein Synthesis During Sleep and Memory Consolidation

本项目涉及的协议为09-M-0123， NCT00884702。

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.