Orexinergic innervations at GABAergic neurons of the lateral habenula mediates the anesthetic potency of sevoflurane
CNS NEUROSCIENCE & THERAPEUTICS(2023)
Abstract
AimsThe circuitry mechanism associated with anesthesia-induced unconsciousness is still largely unknown. It has been reported that orexinergic neurons of the lateral hypothalamus (LHA) facilitate the emergence from anesthesia through their neuronal projections to the arousal-promoting brain areas. However, the lateral habenula (LHb), as one of the orexin downstream targets, is known for its anesthesia-promoting effect. Therefore, the current study aimed to explore whether and how the orexinergic projections from the LHA to the LHb have a regulatory effect on unconsciousness induced by general anesthesia. MethodsWe applied optogenetic, chemogenetic, or pharmacological approaches to regulate the orexinergic(LHA-LHb) pathway. Fiber photometry was used to assess neuronal activity. Loss or recovery of the righting reflex was used to evaluate the induction or emergence time of general anesthesia. The burst-suppression ratio and electroencephalography spectra were used to measure the anesthetic depth. ResultsWe found that activation of the orexinergic(LHA-LHb) pathway promoted emergence and reduced anesthetic depth during sevoflurane anesthesia. Surprisingly, the arousal-promoting effect of the orexinergic(LHA-LHb) pathway was mediated by excitation of glutamate decarboxylase (GAD2)-expressing neurons, but not glutamatergic neurons in the LHb. ConclusionThe orexinergic(LHA-LHb) pathway facilitates emergence from sevoflurane anesthesia, and this effect was mediated by OxR2 in GAD2-expressing GABA neurons.
MoreTranslated text
Key words
GAD2-expressing neuron,general anesthesia,lateral habenula,orexin,sevoflurane
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined