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结合有关。这个项目检验了这样一种假设，即睡眠在引导昼夜行为方面起主导作用，并且在遗传水平上存在促进睡眠表达和睡眠状态对昼夜行为影响的相互作用。一个工作模型确定了来自产生状态的中脑区的5-羟色胺和/或胆碱能传入输入的潜在影响，作为影响视交叉上核(SCN)神经元激活和随后的昼夜行为的机制。设计方案是为了描述两个近交系小鼠的睡眠和昼夜行为的昼夜节律，这两个品系的小鼠在相关的睡眠、昼夜和/或神经行为特征上存在差异。在量化了自发发生的睡眠和昼夜行为模式后，每个菌株都将接受标准化的干预，限制或诱导矛盾的睡眠，以确定基因和环境对睡眠和随后的昼夜行为的影响。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(呼吸频率、心率和代谢率)，以及与昼夜体温和活动节律的相关性，作为紧张和干预的因变量(方差分析)。一些但不是所有的衡量标准在一个品系内的差异比在品系之间的差异要小，这表明给定性状变量的遗传成分。第二组结果指标将是对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的神经组织学评估。通过顺行追踪和与神经递质表型的共同定位，将研究不同菌株向SCN核的传入投射的差异。该项目的一个组成部分是简化仪器设备，设计对睡眠和昼夜行为的微创监测。这些发现将放大睡眠作为SCN功能的内在修饰物这一新假设，并发现与睡眠有关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.