Global changes in synaptic strength and excitability during sleep andwakefulness

睡眠和清醒期间突触强度和兴奋性的整体变化

基本信息

批准号：
7839761
负责人：
JOSEPH R. FETCHO
金额：
$ 79.5万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2014-07-31
项目状态：
已结题

项目摘要

DESCRIPTION Abstract Sleep and sleep states are fundamental not only to human life, but to every animal with a nervous system. Surprisingly, it is still not clear why they are so important. One compelling idea is that there are global shifts in the strengths of synaptic connections and excitability during sleep that act to keep synaptic function and neuronal excitability in a range where synapses and excitability of neurons can change relative to one another to allow for learning. If this does not happen, network function and behavior, whether in a worm or a human, degrade, leading ultimately to death. Such thinking about an important role of homeostatic mechanisms is moving to the fore in neuroscience, but what is needed to test hypotheses about global patterns of change in synapses and excitability is a model system and tools that allow us to monitor single synapses and neurons broadly in the living brain. We propose to develop and apply optical tools that allow us to examine patterns of scaling of synapses and excitability in the transparent zebrafish model where we can monitor these regularly and non-invasively over time during sleep and wakefulness. We will use these to directly test whether global resetting occurs during sleep. If sleep really involves such rescaling, the implications would be major, not only for a basic understanding of sleep, something that we should understand by now, but also for trying to restore functional states when sleep is impaired as a result of sleep disorders. Public Health Relevance Disorders of sleep are a major health problem, but we do not yet even understand the events that occur during sleep that make it so critical for brain function. We propose to explore global patterns of changes in synaptic strengths and neuronal excitability during sleep to test ideas that some phases of sleep are important for a broad resetting of synaptic strengths and neuronal excitability. Without sleep, a degradation of brain function ensues, leading ultimately

描述抽象的睡眠和睡眠状态不仅对人类的生命是基本的，而且对每个具有神经系统的动物都是基本的。令人惊讶的是，仍然不清楚为什么它们如此重要。一个引人注目的想法是，在睡眠期间，突触连接和兴奋性的强度存在全球变化，以使突触功能和神经元兴奋性保持在突触和神经元的突触和兴奋性相对于彼此之间的变化以允许学习的范围内。如果没有发生这种情况，则是网络功能和行为，无论是在蠕虫还是人类中，都会降解，最终导致死亡。关于稳态机制的重要作用的这种思考在神经科学中转向脱颖而出，但是测试关于突触和兴奋性全球变化模式的假设所需的是模型系统和工具，使我们能够在活体大脑中广泛监测单个突触和神经元。我们建议开发和应用光学工具，使我们能够在透明的斑马鱼模型中检查突触缩放和兴奋性的模式，在那里我们可以在睡眠和清醒期间定期和非侵入性地监测这些模式。我们将使用这些直接测试在睡眠期间是否发生全局重置。如果睡眠确实涉及这种恢复，那么含义将是重大的，不仅是对睡眠的基本理解，这是我们现在应该理解的，而且在由于睡眠障碍而损害睡眠时试图恢复功能状态。公共卫生相关性睡眠疾病是一个主要的健康问题，但我们甚至还不了解睡眠期间发生的事件，使其对大脑功能如此重要。我们建议探索在睡眠期间突触强度和神经元兴奋性变化的全球模式，以测试某些睡眠阶段对于广泛重置突触强度和神经元兴奋性很重要。没有睡眠，随之而来的大脑功能降解，最终导致