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
Affiliations
Yan Wang
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xin Song Jiang Road, Shanghai 201620, China
Ling Xu
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xin Song Jiang Road, Shanghai 201620, China
Ming-Zhe Liu
Department of Respiratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
Dan-Dan Hu
Tongji University School of Medicine, Shanghai, China
Fang Fang
Department of Endocrinology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
Dao-Jie Xu
Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China
Rui Zhang
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xin Song Jiang Road, Shanghai 201620, China
Xiao-Xiao Hua
Tongji University School of Medicine, Shanghai, China
Jin-Bao Li
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xin Song Jiang Road, Shanghai 201620, China
Ling Zhang
Tongji University School of Medicine, Shanghai, China
Li-Na Huang
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xin Song Jiang Road, Shanghai 201620, China; Corresponding author
Di Mu
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xin Song Jiang Road, Shanghai 201620, China; Corresponding author
Summary: 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.