DEVELOPMENT OF SLEEP HOMEOSTASIS IN THE DEVELOPING RAT

描述(改编自申请人的摘要)：本提案将 研究动态平衡睡眠机制的发展和出现 新生大鼠明显的觉醒状态。唤醒状态不能 在出生后发育早期通过脑电参数识别，因此，唤醒 新生儿的状态在行为上被定义为活跃睡眠(AS)和安静 睡眠(QS)。AS和QS通常被认为与REM和NREM同源 然而，在成年人睡眠中，我们发现脑电慢波活动(SWA)发生 与出生后第12天的QS一样频繁(P12)。因此，正如可能的 不是成人快速眼动睡眠的不成熟形式，相反，它可能是一种 神经系统的未分化状态，从中产生非快速眼动睡眠 首先是快速眼动睡眠，其次是快速眼动睡眠。我们将通过确定以下内容来检验这一假设 当附加的生理参数(例如，呼吸模式， 眼电(EOG)、脑和皮肤温度以及肌阵挛) 结合并形成可识别的唤醒状态。我们已经开发了一个系统 用于同时记录脑电、肌电和行为睡眠(通过录像带) 在新生大鼠中，从P12持续到P30。我们发现了像成年人一样的 对睡眠剥夺(SD)的反应直到P24才出现； 在这个年龄，SD会导致总睡眠时间(TST)增加，而不会影响 SWA的强度或数量。从P12-P24，SWA递增 超过成人水平，但不受SD影响。因此，关键组件 在P24之前，必须没有成人睡眠的动态平衡机制。 一致的证据支持腺苷在调节SWA中的作用； 然而，它与体内平衡机制的联系尚不清楚。我们发现， 腺苷A受体激动剂N6-环戊基腺苷(CPA)模拟 SD对成年和新生大鼠的影响。此外，CPA还引发了SWA 在SD处理3h的日龄(P16和P20)，SWA无明显变化。因此，A1 受体存在并发挥作用，但显然不能被SD激活。 这项建议将研究觉醒状态的出现、睡眠的发展 新生儿睡眠动态平衡及其腺苷能调节 老鼠。这些研究将对临床研究做出重大贡献。 关于婴儿猝死综合症(SID)，因为他们调查了 从睡眠中唤醒并因此而无法唤醒的机制 发展。

DESCRIPTION (Adapted from applicant's abstract): This proposal will investigate the development of homeostatic sleep mechanisms and emergence of distinct arousal states in the neonatal rat. Arousal states cannot be identified by EEG parameters early in postnatal development, thus, arousal states in neonates are defined behaviorally as active sleep (AS) and quiet sleep (QS). AS and QS are generally considered homologous to REM and NREM sleep in adults, however, we found that EEG slow wave activity (SWA) occurs as often during AS as it does in QS at postnatal day 12 (P12). Thus, AS may not be an immature form of adult REM sleep, rather, it may be an undifferentiated state of the nervous system out of which NREM sleep emerges first and REM sleep second. We will test this hypothesis by determining when additional physiological parameters (e.g., respiratory patterns, electro-oculogram (EOG), brain and skin temperatures, and myoclonia) coalesce and form identifiable arousal states. We have developed a system for simultaneous recording of EEG, EMG, and behavioral sleep (by videotape) in neonatal rats continuously from P12 to P30. We found that adult-like responses to sleep deprivation (SD) were not present until P24; prior to that age, SD elicits increases in total sleep time (TST) without affecting the intensity or amount of SWA. From P12-P24, SWA increases progressively beyond adult levels, yet is not affected by SD. Thus, critical components of adult sleep homeostatic mechanisms must be absent prior to P24. Convergent lines of evidence support a role for adenosine in regulating SWA; however, its link to homeostatic mechanisms is unknown. We found that the adenosine A~ receptor agonist, N6-Cyclopentyladenosine (CPA), mimics the effects of SD in both adult and neonatal rats. Furthermore, CPA elicits SWA at ages (P16 and P20) when 3 h of SD have no effect on SWA. Thus, A1 receptors are present and functional but apparently not activated by SD. This proposal will investigate arousal state emergence, development of sleep homeostasis, and adenosinergic regulation of sleep homeostasis in neonatal rats. These studies will contribute significantly toward clinical studies on sudden infant death syndrome (SIDS) because they investigate the mechanisms by which arousal and, hence, failure to arouse, from sleep develop.