Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Modulate the Anesthetic Potency of Isoflurane in Mice
Shiyi Zhao1 • Rui Li1 • Huiming Li1 • Sa Wang1 • Xinxin Zhang1 • Dan Wang1 • Juan Guo1 • Huihui Li1 • Ao Li1 • Tingting Tong1 • Haixing Zhong1 • Qianzi Yang1 • Hailong Dong1
1 Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
Abstract
The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.
Keywords
Anesthesia; Isoflurane; Lateral hypothalamic area; Lateral habenula; Glutamatergic neuron
