The locus coeruleus (LC), which is located in the brain stem, plays an important role in promoting arousal. However, the neural circuitry underlying this function remains unclear. Using cortical electroencephalography combined with optrode recording, we found that LC noradrenergic (LC^NA) neurons exhibit high activity during wakefulness, while suppressing the activity of these neurons causes a reduction in wakefulness. Viral tracing showed that LC^NA neurons directly project to the ventrolateral preoptic area (VLPO) and that optogenetic activation of the noradrenergic (NAergic) LC-VLPO (NAergic^LC-VLPO) neural circuit promotes arousal. Optrode recordings in the VLPO revealed two functionally distinct neuronal populations that were stimulated in response to the optogenetic activation of LC^NA neurons. Consistently, we identified two types of VLPO neurons that exhibited different responses to NAergic projections from the LC mediated by discrete adrenergic receptors. Together, our results demonstrate that the NAergic^LC-VLPO neural circuit is a critical pathway for controlling wakefulness and that a synergistic effect is produced by inhibition of sleep-active neurons in the VLPO through α₂ receptors and activation of wake-active neurons in the VLPO through α₁ and β receptors.

位于脑干中的蓝斑（LC）在促进觉醒中起重要作用。然而，该功能背后的神经回路仍不清楚。使用皮层脑电图结合光极记录，我们发现 LC 去甲肾上腺素能 (LC ^NA ) 神经元在清醒时表现出高活性，而抑制这些神经元的活动会导致清醒度降低。病毒追踪显示 LC ^NA神经元直接投射到腹外侧视前区 (VLPO)，并且去甲肾上腺素能 (NAergic) LC-VLPO (NAergic ^{LC-VLPO ) 的光遗传学激活}) 神经回路促进唤醒。VLPO 中的光极记录揭示了两个功能不同的神经元群，它们响应 LC ^NA神经元的光遗传学激活而受到刺激。一致地，我们确定了两种类型的 VLPO 神经元，它们对由离散肾上腺素能受体介导的 LC 的 NAergic 投射表现出不同的反应。总之，我们的结果表明，NAergic ^LC-VLPO神经回路是控制清醒的关键途径，并且通过 α ₂受体抑制 VLPO 中的睡眠活跃神经元和激活 VLPO 中的唤醒活跃神经元产生协同效应。 VLPO 通过 α ₁和 β 受体。