Sleep Function and Synaptic Homeostasis: Linking Neurobiology and Mental Health

睡眠功能和突触稳态：神经生物学和心理健康的联系

• 批准号: 7650161
• 负责人: GIULIO TONONI
• 金额: $ 96.15万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7650161
• 关键词: Sleep; Function; Synaptic; Homeostasis; Linking

DESCRIPTION (Provided by applicant): This application requests four years of funding to establish a Conte Center to Develop Collaborative Neuroscience Research. Through the Center, we intend to test a comprehensive, novel hypothesis about the function of sleep - the synaptic homeostasis hypothesis. The hypothesis states that plastic processes during wakefulness result in a net increase in synaptic strength in many brain circuits, leading to increased metabolic consumption. Strengthened brain circuits then lead to larger slow waves during subsequent sleep. In turn, sleep slow waves renormalize synaptic strength to a baseline level that is energetically sustainable and beneficial for memory and performance. Sleep is therefore the price we pay for plasticity, and its function is the homeostatic regulation of the total synaptic weight impinging on neurons. The hypothesis accounts for many facts about sleep and its regulation and makes intriguing predictions that are relevant for both basic and clinical neuroscience. We propose to test such predictions through four tightly linked and complementary projects, to be carried out jointly at the University of Wisconsin and at Washington University. Project I (PI Cirelli) employs a combined molecular / electrophysiological approach in an animal model to establish a relationship between synaptic potentiation during waking, an increase in sleep slow waves, and the resulting synaptic renormalization; Project II (PI Tononi) employs behavioral / high-density (hd)-EEG paradigms in healthy human subjects to determine whether learning leaves a local EEC trace in both wakefulness and sleep, and to determine whether sleep slow waves are necessary to renormalize this trace; Project III (PI Raichle) employs the same behavioral paradigms in conjunction with PET and fMRI to investigate whether learning leaves a local metabolic trace that is renormalized by sleep; and Project IV (PI Benca) employs the same behavioral / hd-EEG paradigms in patients with major depression to evaluate a predicted relationship between preserved slow wave homeostasis and therapeutic response to sleep deprivation. If the hypothesis survives these combined tests, it will provide a scientific explanation of why we need to sleep that ranges all the way from molecular and cellular function to systems neurophysiology and neuroimaging. Given the central role of sleep in the life of every organism, at every age, we expect that the results of our program will have major implications for many aspects of human health and disease.

描述（由申请人提供）：本申请要求为期四年的资金建立孔戴中心以开发合作性神经科学研究。通过中心，我们打算检验一个关于睡眠功能的全面，新颖的假设 - 突触稳态假设。该假设指出，清醒期间的塑性过程导致许多脑回路的突触强度净增加，从而导致代谢消耗增加。加强大脑回路，然后在随后的睡眠期间导致较大的慢波。反过来，睡眠慢波将突触强度恢复到基线水平，在能量可持续性且对记忆和性能上有益。因此，睡眠是我们为可塑性支付的价格，其功能是对神经元撞击的全部突触重量的体内调节。该假设解释了有关睡眠及其调节的许多事实，并做出了与碱性和临床神经科学相关的有趣预测。我们建议通过在威斯康星大学和华盛顿大学共同进行的四个紧密联系和互补项目来测试此类预测。项目I（Pi Cirelli）在动物模型中采用了一种组合分子 /电生理方法，以在醒来过程中建立突触增强，睡眠慢波的增加与由此产生的突触重态化之间的关系；项目II（PI TONONI）在健康人类受试者中采用行为 /高密度（HD）-EEG范式，以确定学习是否在觉醒和睡眠中留下局部EEC痕迹，并确定是否需要慢性睡眠，以使此轨迹重新构成这种迹象; III（PI RAICHLE）与PET和FMRI结合使用相同的行为范式来研究学习是否会留下由睡眠重新归一致的局部代谢痕迹； Project IV（PI BENCA）在严重抑郁症患者中采用相同的行为 / HD-EEG范式，以评估保留的慢波稳态与对睡眠剥夺的治疗反应之间的预测关系。如果假设幸存下来这些合并的测试，它将提供一个科学的解释，说明为什么我们需要睡觉，从分子和细胞功能到系统神经生理学和神经影像学。鉴于睡眠在每个生物的生活中的核心作用，在每个年龄段，我们希望我们计划的结果对人类健康和疾病的许多方面都有重大影响。