The NAergic locus coeruleus-ventrolateral preoptic area neural circuit mediates rapid arousal from sleep

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.