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

• 批准号: 7939858
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7939858
• 关键词: Animals; Behavior; Biological Models; Brain; Cessation of life; Event; Global Change; Health; Human; Learning; Life; Modeling; Monitor; Nervous system structure; Neurons; Neurosciences; Optics; Pattern; Phase; Relative (related person); Role; Sleep; Sleep Disorders; Synapses; Testing; Thinking; Time; Wakefulness; Zebrafish; abstracting; neuronal excitability; public health relevance; synaptic function; tool

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

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