SLEEP AND ENTERTAIMENT OF SCN FUNCTION

睡眠-觉醒周期的一个重要特征与它是否以及如何与昼夜节律相关联有关。 该项目研究了睡眠在诱导昼夜节律行为中起主导作用的假设，并且在遗传水平上存在相互作用，促进睡眠的表达和睡眠状态对昼夜节律行为的影响。 一个工作模型确定了来自产生状态的中脑区域的血清素能和/或胆碱能传入输入的潜在影响，作为影响视交叉上核（SCN）神经元激活和随后昼夜节律行为的机制。 方案被设计成表征在相关睡眠、昼夜节律和/或神经行为特征方面不同的两个近交系小鼠的睡眠和昼夜节律行为的昼夜节律。 在对自发发生的睡眠模式和昼夜节律行为进行量化后，每种菌株将接受限制或诱导异相睡眠的标准化干预，以确定基因与环境对睡眠和随后的昼夜节律行为的影响。 测量将包括睡眠结构（睡眠开始、睡眠阶段、睡眠持续时间）及其生理相关性（呼吸率、心率和代谢率），以及与昼夜体温和活动节律的相关性，作为与紧张和干预有关的因变量（方差分析）。 一些但不是所有的措施将在一个菌株内比菌株之间的差异更小，这表明一个给定的性状变量的遗传成分。 第二组结果指标将是神经组织学评价，以了解干预措施如何影响反映SCN和中脑区域神经元激活和神经递质表达的蛋白质表达。 将通过顺行束追踪和与神经递质表型的共定位来研究菌株之间传入投射到SCN核的差异。 该项目的一个组成部分是简化仪器和工程师对睡眠和昼夜行为的微创监测。 研究结果将放大新的假设，即睡眠作为SCN功能的内在修饰剂，并发现睡眠中涉及的生理特征和神经解剖结构的遗传和环境基础的线索。

An important feature of the sleep-wake cycle relates to if and how it is coupled to circadian rhythm. This project examines the hypothesis that sleep has a dominant role in entraining circadian behavior and that there are interactions at a genetic level that promote both the expression of sleep and the effects of sleep state on circadian behavior. A working model identifies the potential influences of serotonergic and/or cholinergic afferent input from state-producing mid-brain regions as mechanisms affecting activation of neurons in the suprachiasmatic nucleus (SCN) and subsequent circadian behavior. Protocols are designed to characterize diurnal rhythms in sleep and circadian behavior in two in-bred strains of mice that differ in relevant sleep, circadian, and/or neurobehavioral characteristics. After quantitification of spontaneously occurring patterns of sleep and circadian behavior, each strain will undergo standardized interventions with restriction or induction of paradoxical sleep to identify gene-by-environment effects on sleep and subsequent circadian behavior. Measures will include sleep architecture (sleep onset, sleep stages, sleep duration), and its physiologic correlates (respiratory rate, heart rate, and metabolic rate), with correlation to diurnal body temperature and activity rhythms, as dependent variables in regard to strain and to intervention (analysis of variance). Some but not all measures will differ less within a strain than between strains, indicating a genetic component to a given trait variable. A second set of outcome measures will be a neurohistologic evaluation of how interventions affect the expression of proteins that reflect neuronal activation and neurotransmitter expression in the SCN and mid-brain regions. Differences among strains in afferent projections to SCN nuclei will be studied by anterograde tract tracing and co-localization with neurotransmitter phenotype. A component of the project is to simplify the instrumentation and engineer minimally invasive monitoring of sleep and circadian behavior. Findings will amplify the novel hypothesis that sleep acts as an intrinsic modifier of SCN function and to discover clues to the genetic and environmental foundations for physiologic traits and neuroanatomic structures involved in sleep.