Yunyun Zhang1,2 · Sa Wang1,2 · Haonan Li1,2 · Xinxin Zhang1,2 · Dan Wang1,2 · Ye Wang1,2 · Weichao Bai1,2 · Zefei Zhang1,2 · Guangchao Zhao1,2 · Tingting Gu1,2 · Hailong Dong1,2 · Qianzi Yang2,3

1 Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China 

2 Key Laboratory of Anesthesiology, Ministry of Education of China, The Fourth Military Medical University, Xi’an 710032, China 

3 Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Abstract

Dexmedetomidine (DEX) induces a distinct state of “arousable sedation,” yet the neural circuits that sustain arousal capacity remain unclear. Here, we identified that 40 μg/kg DEX produced sedation from which animals could be transiently aroused by tactile stimulation of the back, whereas 100 μg/kg induced deeper, unresponsive sedation. Functional mapping revealed selective activation of the central medial thalamus (CMT). Fiber photometry further confirmed that DEX dose-dependently and selectively activated glutamatergic neurons in the CMT while simultaneously suppressing activity in other thalamic regions. Chemogenetic inhibition of CMT glutamatergic neurons deepened DEX sedation and impaired tactile‑stimulation-induced arousal following administration of 40 μg/kg DEX, whereas activation of CMT glutamatergic neurons under a high-dose DEX (100 μg/kg) attenuated sedation and restored tactile responsiveness. Together, these results establish the CMT as a critical thalamic node for maintaining arousal capacity during DEX sedation.

Keywords

Dexmedetomidine; Arousable sedation; Central medial thalamus; Thalamocortical circuits; Consciousness

[SpringerLink]