SYSTEM FOR AUTOMATED NONINVASIVE MONITORING OF MOUSE SLEEP AND BEHAVIOR

 描述(申请人提供)：睡眠的基本功能尚不清楚。异常睡眠模式可表现为各种障碍-睡眠呼吸暂停、睡眠不良、REM(快速眼动睡眠)行为障碍(RBD)、嗜睡症-其中许多受遗传影响。在遗传学和药物研究中，对小鼠行为的研究越来越受到重视。然而，发现导致睡眠和相关疾病的基因需要耗时的大规模表型行为筛选，以将观察到的特征与遗传学联系起来。对小鼠的行为监测通常仅限于活动测量，如视频跟踪、跑轮和光电断束。虽然这些方法中的许多都是非侵入性的，并且具有高通量(HT)应用的潜力，但它们主要监测运动活动，而不提供关于睡眠-觉醒状态和睡眠结构的信息，这对于研究睡眠障碍是重要的。虽然脑电可以准确地确定睡眠-觉醒状态，但它具有侵入性和资源密集性(手术、恢复等)，这限制了其在啮齿动物大规模遗传学研究中的应用。Signal Solutions，LLC开发了一种传感器笼环境，用于非侵入性行为监测，知名研究小组正在使用该环境来识别与睡眠和昼夜节律相关的不同特征的基因。这项工作的具体目标是进一步提高压电系统的非侵入性能力：1.通过将压电信号特征与添加的低成本视频特征分类，将睡眠-觉醒状态(睡眠/觉醒，REM/NREM)和觉醒中的行为(例如，安静与活动、高活动、进食、梳理)区分开来，使其达到与EEG/EMG相当的水平；2.将实时反馈刺激用于行为调整；3.将电子学和新的多模式传感整合到一个紧凑的系统中，用于研究实验室的测试；4.开发低成本的动物福利自动监测设备。设想的最终产品是一个传感器笼和软件接口，用于监测小动物的睡眠-觉醒状态和行为，以确定导致睡眠/昼夜节律紊乱的遗传因素以及药物操作、感觉刺激或神经损伤(例如创伤性脑损伤、癫痫)的行为影响。该系统将特别有利于预先筛选可能感兴趣的表型，并保留侵入性脑电分析以供进一步证实。感兴趣的医学目标是睡眠/昼夜节律紊乱、睡眠呼吸暂停、肥胖/糖尿病、快速眼动/非快速眼动睡眠剥夺和压力等。潜在客户包括对大规模行为监测(例如药物筛选)感兴趣的学术研究实验室和工业实验室。

 DESCRIPTION (provided by applicant): The basic functions of sleep are still unknown. Abnormal sleep patterns can manifest as a variety of disorders- sleep apnea, parasomnias, REM (rapid eye movement sleep) behavioral disorder (RBD), narcolepsy-many of which are influenced by heredity. There is an increasing focus on characterizing mouse behaviors for genetic and drug studies. However, discovering the genes responsible for sleep and related disorders requires time- consuming large-scale behavioral screening of phenotypes to correlate observed traits with genetics. Behavioral monitoring of mice is usually limited to actigraphic measurements such as video tracking, wheel-running, and photoelectric beam-breaking. Although many of these methods are noninvasive and have potential for high- throughput (HT) application, they monitor mainly locomotor activity without providing information about sleep-wake state and sleep architecture, which are important for investigating sleep disorders. While EEG can be used to accurately determine sleep-wake state, it is invasive and resource-intensive (surgery, recovery, etc.), which limits its application in large-scale genetic studies wih rodents. Signal Solutions, LLC, has developed a sensor cage environment for noninvasive behavioral monitoring that is being used by prominent research groups to identify genes responsible for different traits related to sleep and circadian rhythms. The specific aims of this work are to further improve the capabilities of the piezo system to noninvasively: 1. Discriminate sleep-wake state (sleep/wake, REM/NREM) and behavior within wake (e.g., quiet vs. active, high activity, feeding, grooming) to a level comparable to EEG/EMG by classifying piezo signal features with added low-cost video features; 2. Incorporate real-time feedback stimulation for behavior modification, 3. Integrate electronics and with new multimodal sensing into a compact system for testing in research laboratories, 4. Develop low-cost device for automatic animal welfare monitoring. The envisioned end product is a sensor cage and software interface for HT monitoring of sleep-wake state and behavior in small animals to identify genetic factors responsible for sleep/circadian disorders as well as behavioral effects of pharmacological manipulation, sensory stimulation, or neural injury (e.g., traumatic brain injury, epilepsy). This system will be particularly advantageous for prescreening potentially interesting phenotypes, and reserving invasive EEG analysis for further confirmation. Medical targets of interest are sleep/circadian disorders, sleep apnea, obesity/diabetes, REM/NREM sleep deprivation, and stress, among others. Potential clients include academic research labs as well as industrial labs interested in behavioral monitoring on a large scale (e.g., drug screening).