Do single neurons need to sleep and why?

单个神经元需要睡眠吗？为什么？

• 批准号: 8794551
• 负责人: GIULIO TONONI
• 金额: $ 158.35万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8794551
• 关键词: Address; Area; Behavior; Behavioral; Birds; Brain; Brain Part; Brain region; Brain-Derived Neurotrophic Factor; Calcium; Cells; Characteristics; Chemosensitization; Clinical; Cognition; Cognitive; Cognitive deficits; Contralateral; Cortical Column; Disease; Electroencephalography; Epilepsy; Face; Fatigue; Frequencies; Health; Homeostasis; Human; Image; Immobilization; Impaired cognition; Impairment; Individual; Infusion procedures; Lateral; Lead; Learning; Life; Light; Link; Monkeys; Motor Cortex; Mus; Napping; Neurons; Occipital lobe; Organism; Parasomnias; Parietal; Patients; Pattern; Perceptual learning; Performance; Pharmacogenetics; Plastics; Play; Population; Price; Rattus; Regulation; Reporting; Rest; Role; Rotation; Scanning Electron Microscopy; Sleep; Slow-Wave Sleep; Somnambulism; Stimulus; Synapses; Synaptic plasticity; System; Therapeutic Intervention; Time; Training; Vibrissae; Visual; Wakefulness; arm; awake; base; brain cell; cost; density; falls; fascinate; fly; in vivo; neuropsychiatry; public health relevance; response; restoration; single cell analysis; sleep regulation; synaptic depression; voltage

 DESCRIPTION (provided by applicant): Sleep is pervasive, universal, irresistible, tightly regulated, and its loss impairs performance and cognition. Sleep is thought to perform essential restorative functions for the brain, and increasing evidence suggests that sleep may ultimately reflect a local need for homeostasis that is triggered by the cellular consequences of wake, primarily related to the costs of synaptic plasticity associated with learning. This evidence is consistent with the hypothesis that sleep and wake may occur, be regulated, and perform their functions at the level of individual neurons. Recently, using multi-array recordings in freely moving rats, we obtained direct evidence that sleep can occur locally within a group of cortical neurons, while the rest of the brain remains awake, and that such "local sleep" increases with the duration of wake. If so, does local sleep occur in different species, and what are the underlying mechanisms? Are they similar to those governing the regulation of sleep at the systems level? And do they reflect cellular needs for restoration triggered by the progressive accumulation of plastic changes due to learning in wake (neuronal "tiredness") or merely by intense activity ("fatigue")? Moreover, are there cellular/ultrastructural signatures of the cost o wake plasticity for brain cells and, conversely, that sleep has occurred and restored homeostasis? Finally, does the occurrence of local sleep during wake lead to performance impairments, which could explain the performance/cognitive deficits observed in sleep-restricted humans and in some neuropsychiatric disorders? These are fascinating and long-standing questions, and it is finally becoming possible to address them directly by taking advantage of several technological breakthroughs that permit single cell analysis and causal manipulations, including multi-array recordings, high-density (hd) EEG, in vivo calcium imaging, thermo/opto/pharmacogenetics, and serial block- face scanning electron microscopy (SBF-SEM). This proposal includes three highly integrated and complementary projects employing flies (Project I), mice (Project II), and humans (Project III) to address three related questions: . Does local sleep occur in different species, and is it triggered by mechanisms similar to those that trigger sleep proper, or merely by fatigue? 2. What are the cellular/ultrastructural signature of wake plasticity and, conversely, of the restorative functions of sleep? 3. What are the behavioral/cognitive consequences of local sleep in an awake brain?

 描述（由申请人提供）：睡眠是普遍的，普遍的，不可抗拒的，严格的调节，它的损失损害性能和认知。睡眠被认为对大脑具有重要的恢复功能，越来越多的证据表明，睡眠可能最终反映了局部对稳态的需求，这种需求是由觉醒的细胞后果触发的，主要与学习相关的突触可塑性的成本有关。这一证据与睡眠和觉醒可能在单个神经元的水平上发生、调节和执行其功能的假设是一致的。最近，在自由活动的大鼠中使用多阵列记录，我们获得了直接的证据，即睡眠可以在一组皮层神经元内局部发生，而大脑的其他部分保持清醒，并且这种“局部睡眠”随着清醒的持续时间而增加。如果是这样的话，局部睡眠是否发生在不同的物种中，其潜在的机制是什么？它们是否类似于在系统水平上管理睡眠的调节？它们是否反映了细胞对恢复的需求，是由清醒学习（神经元“疲劳”）或仅仅是由强烈活动（“疲劳”）引起的可塑性变化的逐步积累所触发的？此外，是否存在脑细胞清醒可塑性的细胞/超微结构特征，以及相反，睡眠已经发生并恢复稳态？最后，清醒时局部睡眠的发生是否会导致表现障碍，这可以解释在睡眠受限的人类和某些神经精神疾病中观察到的表现/认知缺陷？这些都是迷人的和长期存在的问题，它终于成为可能直接解决他们利用几个技术突破，允许单细胞分析和因果操纵，包括多阵列记录，高密度（hd）脑电图，在体内钙成像，热/光/药物遗传学，和连续块面扫描电子显微镜（SBF-SEM）的优势。该提案包括三个高度综合和互补的项目，使用苍蝇（项目I），小鼠（项目II）和人类（项目III）来解决三个相关问题：局部睡眠发生在不同的物种中，它是由类似于触发睡眠的机制触发的，还是仅仅由疲劳触发的？2.唤醒可塑性的细胞/超微结构特征是什么？相反，睡眠的恢复功能是什么？3.在清醒的大脑中，局部睡眠的行为/认知后果是什么？