FUNCTIONAL ANALYSIS OF SLEEP HOMEOSTASIS IN DROSOPHILA

描述（由申请人提供）：长时间清醒会导致人类、大鼠和苍蝇的认知障碍。睡眠内稳态，即在睡眠不足后观察到的睡眠增加，被认为可以通过恢复在睡眠不足期间退化的重要生物过程来抵消长时间清醒的负面影响。不幸的是，究竟哪些进程需要恢复仍然是一个猜测和争论的问题。考虑到睡眠障碍越来越被认为是神经系统疾病患者认知障碍的原因，识别在清醒时退化而在睡眠中恢复的通路可能会增强我们理解健康和疾病期间神经元过程的能力。我们发现，睡眠不足导致的短期记忆缺陷可以在睡眠剥夺期间逆转到只有在整晚睡眠后才能观察到的水平。具体来说，短期记忆的功能恢复可以通过改变单个神经元结构来实现。考虑到这一点，我们将评估睡眠不足对训练后睡眠剥夺后短期记忆的获得和长期记忆（LTM）巩固能力的作用。我们假设，在睡眠剥夺期间防止短期记忆下降和/或在训练后睡眠剥夺后保持巩固长期记忆能力的基因是在睡眠恢复中发挥作用的强有力候选基因。

DESCRIPTION (provided by applicant): Extended periods of waking result in cognitive impairments in humans, rats, and flies. Sleep homeostasis, the increase in sleep observed following sleep loss, is believed to counter the negative effects of prolonged waking by restoring vital biological processes that are degraded during sleep deprivation. Unfortunately, precisely which processes need restoration remains a matter of speculation and debate. Given that sleep disturbances are increasingly recognized as contributing to cognitive impairment in patients with neurological disorders, identifying pathways that are degraded during waking and restored during sleep may enhance our ability to understand neuronal processes during both health and disease. We have found that short-term memory deficits resulting from sleep loss can be reversed during sleep deprivation to a level only observed following a full night's sleep. Specifically, functional restoration of short-term memory can be achieved in an otherwise wake, behaving animal by altering a single neuronal structure. With that in mind, we will evaluate the role of sleep loss on both the acquisition of short-term memory and the ability to consolidate long-term memories (LTM) after post-training sleep deprivation. We hypothesize that genes that prevent declines in short-term memory during sleep deprivation and/or preserve the ability to consolidate long-term memories LTM after post- training sleep deprivation are strong candidates for playing a role in sleep restoration. PUBLIC HEALTH RELEVANCE: Sleep disturbances are increasingly recognized as contributing to cognitive impairment in patients with neurological disorders. Identifying pathways that are degraded during waking and restored during sleep may enhance our ability to understand neuronal processes during both health and disease.