Norepinephrine modulates wakefulness via α1 adrenoceptors in paraventricular thalamic nucleus

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

doi:10.1016/j.isci.2021.103015

Norepinephrine modulates wakefulness via α1 adrenoceptors in paraventricular thalamic nucleus

iScience. 2021 Aug 21;24(9):103015. doi: 10.1016/j.isci.2021.103015. eCollection 2021 Sep 24.

Authors

Yan Wang¹, Ling Xu¹, Ming-Zhe Liu², Dan-Dan Hu³, Fang Fang⁴, Dao-Jie Xu⁵, Rui Zhang¹, Xiao-Xiao Hua³, Jin-Bao Li¹, Ling Zhang³, Li-Na Huang¹, Di Mu¹

Affiliations

¹ Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xin Song Jiang Road, Shanghai 201620, China.
² Department of Respiratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
³ Tongji University School of Medicine, Shanghai, China.
⁴ Department of Endocrinology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
⁵ Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Abstract

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.

Keywords: Behavioral neuroscience; Biological sciences; Cellular neuroscience; Neuroscience.