CONTROL OF SLEEP AND AROUSAL

控制睡眠和觉醒

• 批准号: 6392752
• 负责人: Noor Alam
• 金额: $ 11.81万
• 依托单位: SEPULVEDA RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-15 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392752
• 关键词: adenosine; arousal; electrodes; electroencephalography; electromyography; extracellular; gamma aminobutyrate; laboratory rat; microdialysis; neurobiology; neurons; neurophysiology; neuropsychology; neuroregulation; prosencephalon; psychobiology; purinergic receptor; sleep; sleep deprivation; wakefulness

DESCRIPTION (adapted from applicant's abstract): Extensive evidence supports the idea that the magnocellular basal forebrain (MBF) plays a critical role in EEG activation and behavioral arousal. Evidence suggests that the onset of non-rapid eye movement (NREM) sleep, in part, involves the inhibition of the arousal mechanism located within the MBF. Adenosine and GABA have been implicated in sleep-regulation and hypothesized to inhibit the MBF arousal system. While putative wake- (WRNs) and sleep-regulating neurons (SRNs) within MBF have been electrophysiologically studied in detail, very little is known about the in vivo neurochemical regulation of these cell types across the sleep-wake cycle in freely moving animals. The proposed experiments will evaluate the contributions of adenosinergic and GABAergic mechanisms in the discharge modulation of WRNs and SRNs in the MBF across sleep-waking states, during sleep-deprivation, and recovery sleep. We hypothesize that adenosine suppresses WRNs in the MBF via A1 adenosine receptors and activates SRNs via A2 adenosine receptors. We hypothesize that GABA-mediated inhibition contributes to the suppression of WRNs in the MBF during NREM sleep. We hypothesize that the extracellular levels of adenosine in the MBF will be higher during waking as compared with sleep. In contrast, extracellular levels of GABA during sleep will be higher than during waking. We hypothesize that extracellular levels of adenosine will increase during short-term sleep deprivation, whereas GABA levels will be higher during recovery sleep. We hypothesize that WRNs in the MBF will exhibit decreased spontaneous discharge during recovery sleep as compared to its baseline. Adenosine and GABA antagonists will partially attenuate changes in neuronal discharge and excitability that occur during sleep deprivation and recovery sleep. The effects of adenosinergic and GABAergic agents on MBF neurons will be studied by combining chronic microwire methods for extracellular unit recording with the delivery of pharmacological agents adjacent to the neurons with a microdialysis probe in freely behaving rats. The extracellular levels of adenosine and GABA in the MBF will be measured across the sleep-wake cycle during sleep-deprivation and recovery sleep. These pharmacological manipulations and analytical procedures will help understanding of the adenosinergic and GABAergic mechanisms that shape the discharge patterns of the MBF neurons across the sleep-waking cycle.

描述(改编自申请者摘要)：广泛的证据支持 认为大细胞基底前脑(MBF)在 脑电激活和行为唤醒。有证据表明， 非快速眼动(NREM)睡眠在一定程度上涉及到对 觉醒机制位于MBF内。腺苷和GABA一直是 与睡眠调节有关，并被假设为抑制MBF唤醒 系统。而推测的觉醒(WRN)和睡眠调节神经元(SRN)在 对MBF进行了详细的电生理研究，但知之甚少。 关于这些细胞类型在体内的神经化学调节 自由活动动物的睡眠-觉醒循环。拟议中的实验将 评价腺苷能和GABA能机制在脑出血中的作用 跨睡眠唤醒状态对MBF中的WRN和SRN的放电调制， 在睡眠剥夺和恢复睡眠期间。我们假设腺苷 通过A1腺苷受体抑制MBF中的WRNS，通过A2激活SRN 腺苷受体。我们假设GABA介导的抑制作用 与NREM睡眠期间MBF中WRN的抑制有关。我们假设 在清醒时，MBF中的细胞外腺苷水平会更高 与睡眠相比。相比之下，睡眠期间细胞外的GABA水平 会比醒着的时候高。我们假设细胞外水平的 在短期睡眠剥夺期间，腺苷会增加，而GABA 在恢复睡眠期间，血药浓度会更高。我们假设世界上的WRN 在恢复睡眠期间，MBF的自发放电会减少，因为 与它的基线相比。腺苷和GABA拮抗剂将部分 减弱神经元放电和兴奋性的变化 睡眠剥夺和恢复睡眠。腺苷能神经递质的作用 GABA能药物对MBF神经元作用的研究将结合慢性微丝 药物递送的细胞外单位记录方法 用微渗析探头与神经元相邻的药物自由活动 老鼠。MBF中的腺苷和GABA的胞外水平将是 在睡眠剥夺和恢复期间测量睡眠-觉醒周期 睡吧。这些药理操作和分析程序将会有所帮助 对腺苷能和GABA能机制的理解 睡眠-觉醒周期中MBF神经元的放电模式。