Development of Automated Noninvasive DiskTreadmills for Sleep Deprivation in Mice

描述(由申请者提供)：6.项目摘要-现代社会面临着一种日益严重的流行病，这种流行病遍及所有年龄段：每天睡眠不足。累积睡眠不足会导致白天过度困倦，并损害认知能力。它带来的诸多经济和物质后果包括：工作生产率下降和汽车事故率上升。临床医生越来越多地注意到睡眠不足对心血管、代谢、内分泌和精神功能的负面影响。这个国家日益增长的“睡眠债”最近在媒体上引起了极大的关注。然而，虽然大多数人类睡眠不足是由慢性睡眠限制(CSR)引起的，但大多数动物研究集中在急性和完全睡眠剥夺上。长期以来，建立CSR动物模型的技术困难一直阻碍着更好地了解长期部分睡眠剥夺的影响。为了极大地改善这种情况，并直接响应PA-06-028中表达的需求，这一STTR应用程序代表着宾夕法尼亚州立大学(PSU)和Afasci，Inc.共同努力，为小鼠开发一种新的非侵入性自动睡眠限制系统，小鼠是研究睡眠障碍的日益重要的物种。PSU最近开发了一种基于脑电(EEG)和肌电(EMG)睡眠检测的圆盘跑步机方法来剥夺小鼠的睡眠。Afasci与斯坦福大学合作，开发了一种非侵入性睡眠检测硬件/软件系统，该系统基于压电膜检测到的运动信号，该压电膜将老鼠笼底部排列在一层薄薄的正常被褥下。我们现在建议通过将EEG/EMG和无创压电睡眠检测与独特设计的圆盘跑步机相结合来创建一种新的设备DiscTreadMillTM。这项拟议的第一阶段项目有三个具体目标：第一，我们将开发一种新的DiscTreadMILL硬件，具有压电传感器和无线数据采集和控制功能，适用于小鼠的脑电/肌电和/或基于压电的睡眠限制。其次，我们将开发软件，可以根据脑电/肌电或压电信号自动对睡眠/觉醒状态进行评分，并控制睡眠剥夺程序。第三，我们将通过同时记录两种不同睡眠模式的小鼠的脑电/肌电和压电信号，来评估和验证DiscTread Mill的有效性和局限性，特别是基于压电的睡眠限制方法。第一阶段的研究将生产出一种独特的工程设计的DiscTad Mill原型设备，并安装特殊的软件。这个创新和多功能的工具包将加速建立慢性睡眠限制动物模型，并帮助打破睡眠研究所需的脑电专业知识的显着障碍。具有替代非侵入性睡眠检测/限制功能的DiscTREADMILL将帮助其他学科的研究人员将他们的特定主题，如心血管、新陈代谢、内分泌免疫学和神经行为领域与基本的睡眠稳态调节联系起来。这种可扩展的仪器最终将促进转基因动物的睡眠行为表型分析和与睡眠障碍治疗相关的药物发现。7.项目叙述现代社会面临着越来越多的“睡眠债”，这已经开始影响公众健康。睡眠不足的累积会导致白天过度困倦，损害认知，并对心血管、新陈代谢、内分泌和精神功能造成长期影响。我们建议开发一种新型的DiscTreadmilTM设备，该设备可以创建慢性睡眠限制的小鼠模型，用于睡眠行为评估和药物开发。这一强大的工具最终将有助于发现治疗睡眠和精神障碍的新靶点和新药。

DESCRIPTION (provided by applicant): 6. Project Summary-Abstract Modern societies face a mounting epidemic that cuts across all age groups: daily sleep loss. Cumulative sleep loss induces excessive daytime sleepiness and impairs cognitive performance. Among its many financial and physical consequences: sinking job productivity and rising auto accident rates. Clinicians increasingly note the negative effects of sleep loss on cardiovascular, metabolic, endocrine, and mental functions. The nation's increasing "sleep debt" has recently received great attention in the media. Yet, while most human sleep loss results from chronic sleep restriction (CSR), most animal studies focus on acute and total sleep deprivation. Technical difficulties in creating CSR animal models have long hindered efforts to better understand the impact of long-term partial sleep deprivation. To greatly improve this situation and directly respond to the need expressed in PA-06-028, this STTR application represents a joint effort from Pennsylvania State University (PSU) and Afasci, Inc., to develop a novel noninvasive automatic sleep restriction system for mice, an increasingly important species for studying sleep disorders. PSU has recently developed a disc-treadmill method to perform sleep deprivation in mice based on electroencephalogram (EEG) and electromyogram (EMG) sleep detection. Afasci, in collaboration with Stanford University, has developed a non-invasive sleep detection hardware/software system based on motion signals detected by a piezoelectric film that lines the mouse cage floor under a thin layer of normal bedding. We now propose to create a new apparatus, DiscTreadmillTM through the integration of EEG/EMG and noninvasive piezo sleep detection with uniquely designed disc-treadmills. This proposed Phase I project has three Specific Aims: First, we will develop a new DiscTreadmill hardware with piezo sensor and wireless data collection and control capabilities adaptable for both EEG/EMG- and/or piezo-based sleep restriction in mice. Second, we will develop software that can automatically score sleep/wake state and control sleep deprivation procedures based on EEG/EMG or piezo signals. Third, we will evaluate and validate DiscTreadmill efficacy and limitation, in particular the piezo-based sleep restriction method, by simultaneously recording EEG/EMG and piezo signals in two strains of mice that have different sleep patterns. The Phase I study will produce a uniquely engineered DiscTreadmill prototype apparatus with special software. This innovative and versatile toolkit will accelerate creating chronic sleep restriction animal models and help break the notable barrier of EEG expertise required in sleep research. The DiscTreadmill with alternative noninvasive sleep detection/restriction will assist researchers from other disciplines to link their specific topics, such as cardiovascular, metabolic, endocrinological immunological, and neurobehavioral areas with the fundamental sleep homeostatic regulation. This scalable instrumentation will ultimately facilitate sleep behavior phenotyping in transgenic animals and drug discovery related to the treatment of sleep disorders. 7. Project narrative Modern society faces an increasing "sleep debt" which has already begun to affect public health. An accumulation of sleep loss causes excessive daytime sleepiness and impairs cognition, as well as causing long-term impacts on cardiovascular, metabolic, endocrine, and mental functions. We propose to develop a novel DiscTreadmillTM apparatus that can create a mouse model of chronic sleep restriction for sleep behavior assessment and drug discovery. This powerful tool ultimately will facilitate discovering new targets and novel drugs to treat sleep and mental disorders.