Global changes in synaptic strength and excitability during sleep andwakefulness

描述 摘要 睡眠和睡眠状态不仅是人类生活的基础，也是每一种有神经系统的动物的基础。令人惊讶的是，人们仍然不清楚为什么它们如此重要。一个令人信服的想法是，睡眠期间突触连接和兴奋性的强度存在全局变化，这有助于将突触功能和神经元兴奋性保持在一个范围内，在这个范围内，突触和神经元的兴奋性可以相对于彼此发生变化，以允许学习。如果不这样做，网络功能和行为，无论是蠕虫还是人类，都会退化，最终导致死亡。这种关于自我平衡机制的重要作用的想法正在神经科学中占据主导地位，但要检验突触和兴奋性的整体变化模式的假设，需要一个模型系统和工具，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，使我们能够检查透明斑马鱼模型中突触和兴奋性的缩放模式，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。我们将使用这些来直接测试在睡眠期间是否发生全局重置。如果睡眠真的涉及到这种重新调整，其意义将是重大的，不仅对于我们现在应该了解的睡眠的基本理解，而且对于试图恢复由于睡眠障碍而导致的睡眠受损的功能状态也是如此。 公共卫生相关性 睡眠障碍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，这些事件对大脑功能至关重要。我们建议探索睡眠过程中突触强度和神经元兴奋性变化的全球模式，以测试睡眠的某些阶段对突触强度和神经元兴奋性的广泛重置很重要的想法。没有睡眠，大脑功能的退化会加剧，最终导致

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