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Norepinephrine modulates wakefulness via a1 adrenoceptors in
AAV-ChR2 was used for optogenetic manipulation. (From BrainVTA)
The viruses used in this article from BrainVTA are in the table below
Optogenetic  PT-0065 AAV2/9-hSyn-Con/Fon-ChR2-EYFP
FLP Recombinase  retroAAV2/2-EF1a-Flpo
Yan Wang, Ling Xu, Ming-Zhe Liu, Dan-Dan Hu, Fang Fang, Dao-Jie Xu, Rui Zhang, Xiao-Xiao Hua, Jin-Bao Li, Ling Zhang, Li-Na Huang, Di Mu
Pub Date: 2021-08-21, DOI: 10.1016/j.isci.2021.103015, Email: [email protected]
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.
In summary, the present study indicates NE modulates wakefulness via a1 adrenoceptors in the PVT. The α1 Ars in the PVT might be a potential central target for understanding wakefulness and general anesthesia mechanisms.
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