Ventrolateral periaqueductal gray GABAergic neurons promote arousal of sevoflurane anesthesia through cortico-midbrain circuit

Yongxin Guo; Yanping Song; Fuyang Cao; Ao Li; Xinyu Hao; Wenzhu Shi; Zhikang Zhou; Jiangbei Cao; Yanhong Liu; Weidong Mi; Li Tong

doi:10.1016/j.isci.2023.107486

Ventrolateral periaqueductal gray GABAergic neurons promote arousal of sevoflurane anesthesia through cortico-midbrain circuit

iScience. 2023 Aug 14;26(9):107486. doi: 10.1016/j.isci.2023.107486. eCollection 2023 Sep 15.

Authors

Yongxin Guo¹, Yanping Song², Fuyang Cao³, Ao Li¹, Xinyu Hao¹, Wenzhu Shi¹, Zhikang Zhou¹, Jiangbei Cao¹, Yanhong Liu¹, Weidong Mi¹, Li Tong¹

Affiliations

¹ Department of Anaesthesiology, The First Medical Centre of Chinese PLA General Hospital, Beijing, China.
² Department of Anaesthesiology, 922th Hospital of Joint Logistics Support Force, PLA, Hengyang, Hunan, China.
³ Department of Anaesthesiology, The Sixth Medical Centre of Chinese PLA General Hospital, Beijing, China.

Abstract

The mechanism of general anesthesia remains elusive. The ventrolateral periaqueductal gray (vlPAG) in the midbrain regulates sleep and awake states. However, the role of vlPAG and its circuits in anesthesia is unclear. We utilized opto/chemogenetics, righting reflex, and electroencephalographic recording to assess consciousness changes. We employed fiber photometry to measure the activity of neurons and neurotransmitters. As a result, photometry recording showed that the activity of GABA neurons in vlPAG decreased during sevoflurane anesthesia and was reactivated after anesthesia. Activating GABAergic neurons in vlPAG promoted arousal during anesthesia, while inhibiting them delayed this process. Furthermore, medial prefrontal cortex (mPFC) to vlPAG pyramidal neurons projections and vlPAG to ventral tegmental area (VTA) GABAergic projections played a prominent role in the anesthesia-awake transition. GABA neurotransmitter activity of VTA synchronized with mPFC-vlPAG pyramidal neuron projections. Therefore, the cortico-midbrain circuits centered on vlPAG GABAergic neurons exert an arousal-promoting effect during sevoflurane anesthesia.

Keywords: Cell biology; Neuroscience; Physiology.