Single unit recording of immunohistcchemically identified hypothalamic sleep waking-promoting neurons

我们记录了免疫组织化学鉴定的下丘脑神经元在头部受限的未麻醉小鼠睡眠-觉醒周期中的自发活动。结节乳头组胺能神经元波从睡眠状态到清醒状态，仅在清醒状态下显示放电，放电率在不同的清醒状态下变化，在安静清醒时最低，在活跃清醒时中等，在触摸尾巴引起的专注清醒时最高。在视前区（POA）记录睡眠特异性神经元。在清醒到困倦状态的过渡阶段，POA睡眠：特定神经元在脑电图同步（睡眠的脑电图标志）开始时或之后开始放电，而组胺能神经元在脑电图同步开始前明显停止放电。在从慢波睡眠到清醒的过渡阶段，POA睡眠特异性神经元在脑电图失同步开始前停止放电，而组胺能神经元在脑电图改变后开始放电的时间更长。下丘脑外侧食欲能神经元表现出清醒-活跃特征，在脑电图失同步和组胺能活动开始前开始放电，并在脑电图同步开始后不久停止放电。在从矛盾睡眠到清醒的过渡阶段，食欲能活动的开始先于肌肉张力的恢复。这些结果表明：1)组胺能神经元的活动是通过食欲能激发来维持的，并参与维持较高水平的警觉性；2)行为状态下的组胺能活动并非完全由POA睡眠促进神经元控制；3)食欲能神经元的活动起着重要的促醒作用，并对抗皮层失活和肌张力丧失。目前的结果也为众所周知的抗组胺药引起嗜睡的现象提供了一致的解释。不幸的是，我们无法尝试直接将药物应用于神经元来阐明每个神经元活动的调节机制，但我们可以获得有意义的发现，并在很大程度上推进了对睡眠-觉醒调节的神经元机制的研究。少

We recorded spontaneous activity of immunohistochemically identified hypothalamic neurons during sleep-waking cycles in the head-restrained unanesthetized mice. The tuberomammillary histaminergic neuronwave sleep to waking, the displayed firing exclusively during wakefulness and the firing rate varied in the different waking states, being lowest during quiet waking, moderate during active waking and highest during attentive waking elicited by touching the tail. Sleep-specific neurons were recorded in the preoptic area (POA). At the transition from waking to drowsy state, POA sleep : specific neurons began firing either at the onset or after the onset of EEG synchronization, the EEG sign of sleep, while histaminergic neurons stopped discharging clearly before the onset of EEG synchronization. At the transition from slow-wave sleep to waking, the POA sleep-specific neurons stopped firing prior to the onset of EEG desynchronization, while histaminergic neurons started firing with a long d … More elay after the EEG change. The lateral hypothalamic orexinergic neuron showed waking-active property, starting discharge prior to the -onset of EEG desynchronization and histaminergic activity, and ceased their firing shortly after the onset of EEG synchronization. At the transition from paradoxical sleep to wakefulness, the onset of orexinergic activity preceded the return of muscle tonus. These results suggest that 1) the activity of histaminergic neurons is maintained through orexinergic excitation and involved in maintenance of a higher level of vigilance, 2) histaminergic activity during behavioral states is not controlled exclusively by POA sleep-promoting neurons, 3) the activity of orexinergic neuron plays an important wake-promoting role and antagonizes cortical deactivation and loss of muscle tone. The present results also provide consistent explanation to the well-known phenomenon that anti-histaminergic drugs cause sleepiness. Unfortunately, we could not try direct application of pharmacological agents to the neuron to elucidate the regulation mechanisms underlying each neuronal activity, but we could obtain meaningful finding and largely advance investigation of neuronal mechanisms of sleep-waking regulation. Less