"Uncoupling sleep deprivation-associated stressors from sleep loss in rodents"

描述（申请人提供）：许多关于脑睡眠机制的结论来自动物睡眠剥夺（SD）实验。然而，动物SD是由动物SD研究中使用的不可控的（从动物的角度来看）厌恶刺激引起的。相比之下，在人体实验中，睡眠不足是自愿的。该项目的总体目标是使用颅内自我刺激（ICSS）作为啮齿动物SD的一种奖励，自我选择的方法，以便将当前动物SD协议中固有的不可控制的厌恶成分的影响与睡眠不足本身的影响分开。我们将比较温和处理SD （GH-SD）、ICSS-SD和施加脑刺激（NCS-SD）对大鼠的影响，使用多导睡眠图、血浆ACTH、皮质酮和催乳素水平，以及持续注意力任务的表现。因此，我们将在sd方法中对每个测量分离出意志和厌恶的贡献。目的1是比较大鼠GH-SD、NCS-SD和ICSS-SD的脑电图和内分泌反应。试验数据表明，ICSS是一种有效的SD处理技术。我们检验假设；1)与GH-SD相比，ICSS-SD和NCS-SD大鼠出现相似的睡眠反弹；2)与NCS-SD和ICSS-SD相比，GH-SD后血浆应激生物标志物表达升高。我们最近的数据表明，gh - sd后在大鼠精神运动警觉性任务（rPVT）上的表现与人类的PVT数据存在重要差异。我们开发了一种新的啮齿动物注意力测试，nRAT。目标2的目标是：1)对比nRAT在每个sd类型后的表现；2)比较SD后与SD人类PVT实验的性能变化。我们验证了与其他SD类型相比，ICSS-SD会导致nRAT的表现缺陷，这种缺陷更能代表人类pvt在SD后发生的表现。拟议的实验将区分不可控的厌恶刺激诱导的脑电图、内分泌和认知反应与睡眠不足诱导的脑电图、内分泌和认知反应。本研究的创新性在于：a)比较了ICSS和GH-SD方法诱导的SD反应，b)开发了一种新的自我强加的动物方法来诱导睡眠缺失，而不需要强迫和厌恶的SD技术，c)改变nRAT中的SD类型，并将结果与人类PVT进行比较；d)验证nRAT作为sd后人类任务时间减少的模型。预期的结果将为动物脑机制研究提供一种新的奖励自我管理SD方法和一种新的认知啮齿动物任务-这是本项目的长期目标。

DESCRIPTION (provided by applicant): Many conclusions about brain sleep mechanisms are derived from animal sleep deprivation (SD) experiments. However, SD in animals is induced by uncontrollable (from the animal's perspective) aversive stimuli used in animal SD studies. In contrast, sleep loss in human experiments is voluntary. The overall goal of this project is to use intracranial self-stimulation (ICSS) as a rewarding, self-chosen method for rodent SD in order to un- couple the effects of the uncontrollable aversive components inherent in current animal SD protocols from the effects of sleep loss per se. We will compare gentle handling SD (GH-SD) vs. ICSS-SD vs. imposed brain stimulation (NCS-SD) in rats using polysomnography, plasma levels of ACTH, corticosterone, and prolactin, and performance on a sustained attention task. Thus, we will isolate the contributions of volition and aversiveness in SD-methods on each measure. The objectives of Aim 1 are to compare rat EEG and endocrine responses in GH-SD, NCS-SD and ICSS-SD. Pilot data show that ICSS is an effective technique for SD. We test the hypotheses that; 1) compared to GH-SD, ICSS-SD and NCS-SD rats will show similar sleep rebound, and 2) plasma expression of stress biomarkers are elevated after GH-SD compared to NCS-SD and ICSS-SD. Our recent data indicate that post-GH-SD performance on the rat psychomotor vigilance task (rPVT) shows important discrepancies with human PVT data. We developed a new rodent attention task, the nRAT. The objectives of Aim 2 are to: 1) contrast nRAT performance after each SD-type; and 2) compare post-SD changes in performance to those from SD human PVT experiments. We test the hypothesis that compared to the other SD-types, ICSS-SD will result in performance deficits in the nRAT that are more representative of performance occurring after SD in the human PVT. The proposed experiments will distinguish between uncontrollable aversive stimuli-induced vs. sleep loss-induced EEG, endocrine and cognitive responses. This proposal is innovative because we: a) compare responses induced by both ICSS and GH-SD methods of SD, b) develop a new self-imposed animal method to induce sleep loss devoid of forced and aversive SD techniques, c) vary SD-types in the nRAT and compare results with human PVT; and d) validate the nRAT as a model of post-SD time-on-task decrements in humans. Anticipated results will provide a new rewarding self-administered SD method and a new cognitive rodent task for use in animal brain mechanism studies -- a long term goal of this project.