CONTROL OF SLEEP AND AROUSAL

描述（改编自申请人摘要）：广泛的证据支持 大细胞基底前脑（MBF）在 脑电图激活和行为唤醒。有证据表明， 非快速眼动（NREM）睡眠，部分涉及抑制 位于MBF内的唤醒机制。腺苷和γ-氨基丁酸 与睡眠调节有关，并假设抑制MBF觉醒 系统而脑内的觉醒（WRN）和睡眠调节神经元（SRN） MBF的电生理学研究已经很详细，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-觉醒周期。拟议的实验将 评价腺苷能和GABA能机制在 在睡眠-觉醒状态下MBF中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WRN，并通过A2激活SRN 腺苷受体。我们假设GABA介导的抑制有助于 与NREM睡眠期间MBF中WRN的抑制有关。我们假设 醒着时MBF中腺苷的细胞外水平会更高 与睡眠相比。相反，睡眠期间细胞外的GABA水平 会比清醒时高我们假设细胞外的 腺苷在短期睡眠剥夺期间会增加，而GABA 在恢复睡眠期间会更高。我们假设， 在恢复睡眠期间，MBF将表现出减少的自发放电， 与基线相比。腺苷和GABA拮抗剂将部分地 减弱神经元放电和兴奋性的变化， 睡眠剥夺和恢复睡眠。腺苷能和 GABA能药物对MBF神经元的作用将结合慢性微导丝进行研究。 记录细胞外单位的方法 用微透析探针在神经元附近自由活动 大鼠MBF中腺苷和GABA的细胞外水平将被测定。 在睡眠剥夺和恢复期间的睡眠-觉醒周期中测量 睡吧这些药理学操作和分析程序将有助于 了解腺苷能和GABA能机制，塑造了 MBF神经元在睡眠-觉醒周期中的放电模式。

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.