Norepinephrine modulates wakefulness via α1 adrenoceptors in paraventricular thalamic nucleus

Norepinephrine (NE) neurons in the locus coeruleus (LC) play key roles in modulating sleep and wakefulness. Recent studies have revealed that the paraventricular thalamic nucleus (PVT) is a critical wakefulness-controlling nucleus in mice. However, the effects of NE on PVT neurons remain largely unknown. Here, we investigated the mechanisms of NE modulating wakefulness in the PVT by using viral tracing, behavioral tests, slice electrophysiology, and optogenetics techniques. We found that the PVT-projecting LC neurons had few collateral projections to other brain nuclei. Behavioral tests showed that specific activation of the LC-PVT projections or microinjection of NE into the PVT accelerated emergence from general anesthesia and enhanced locomotion activity. Moreover, brain slice recording results indicated that NE increased the activity of the PVT neurons mainly by increasing the frequency of spontaneous excitatory postsynaptic currents via α1 adrenoceptors. Thus, our results demonstrate that NE modulates wakefulness via α1 adrenoceptors in the PVT.