The Lateral Habenular Nucleus Is Involved In The Arousal Promoting Effect Of Ketamine

Background and objective: Ketamine is a commonly used intravenous anaesthetic in clinical practice.Studies have found that in the process of using isoflurane to anaesthetize rats,intraperitoneal injection of sub-anaesthetic doses of ketamine can significantly increase the burst suppression rate(BSR)of the rat’s EEG and deepen the anaesthesia.but ketamine can significantly shorten the anaesthetic awakening time of rats.The mechanism of this contradictory phenomenon is still unknown.This study mainly explores the mechanism by which ketamine plays a role in promoting arousal.Methods: 1.Divide 32 8-week-old healthy adult male Vglut2-Cre mice into 4 groups,each with 8 mice.They are h M4Di-CNO group,h M4Di-Control group,h M3Dq-CNO group and h M3Dq-Control group.After the virus was expressed for two weeks,CNO was used to inhibit or activate the Lateral Habenula(LHb)and the time for each group of mice to recover their righting reflex after 40 minutes of anesthesia was recorded.2.Use in vitro electrophysiological techniques to record the effects of ketamine on the neuronal activity of the lateral habenular nucleus of mice under normal conditions.3.Record the effect of activation of lateral habenular nucleus neurons on the EEG burst inhibition ratio during awakening from anesthesia.4.Divide the h M3 Dq receptorexpressing mice into Ketamine-CNO group,Ketamine-Control group and Control group,and observe whether activating lateral habenular nucleus neurons will block the wakefulness-promoting effect of ketamine.Results: 1.Activation of LHb leads to prolonged awakening time from anesthesia(h M3Dq-CNO group: 976±155s,h M3Dq-Control group: 633±161s;P<0.01;N=8),and inhibition of LHb leads to shorter awakening time from anesthesia(h M4Di-Control group: 617±89s,512±85s in h M4Di-CNO group;P<0.05;N=8).2.Ketamine has an inhibitory effect on LHb under normal conditions.3.Activation of LHb resulted in an increase in BSR of EEG during anesthesia awakening(P<0.05;N=7).4.Activation of LHb blocked the wakefulness-promoting effect of ketamine(Ketamine-CNO group:641±52s;Ketamine-Control group: 524±56s;Control group 675±139s;N=6)Conclusion: 1.LHb neurons are involved in the awakening process of isoflurane anesthesia.Inhibiting LHb neurons can promote the anesthesia recovery of mice,and activating LHb neurons will lead to prolonged anesthesia recovery time.2.The inhibitory effect of ketamine on LHb neurons is an important reason for ketamine to promote anesthesia awakening.