GABAergic neurons of anterior thalamic reticular nucleus regulate states of consciousness in propofol‐ and isoflurane‐mediated general anesthesia

Abstract Background The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially the arousal stage of general anesthesia (GA). But the function of thalamus in GA‐induced loss of consciousness (LOC) is little known. The thalamic reticular nucleus (TRN) is the only GABAergic neurons‐composed nucleus in the thalamus, which is composed of parvalbumin (PV) and somatostatin (SST)‐expressing GABAergic neurons. The anterior sector of TRN (aTRN) is indicated to participate in the induction of anesthesia, but the roles remain unclear. This study aimed to reveal the role of the aTRN in propofol and isoflurane anesthesia. Methods We first set up c‐Fos straining to monitor the activity variation of aTRN PV and aTRN SST neurons during propofol and isoflurane anesthesia. Subsequently, optogenetic tools were utilized to activate aTRN PV and aTRN SST neurons to elucidate the roles of aTRN PV and aTRN SST neurons in propofol and isoflurane anesthesia. Electroencephalogram (EEG) recordings and behavioral tests were recorded and analyzed. Lastly, chemogenetic activation of the aTRN PV neurons was applied to confirm the function of the aTRN neurons in propofol and isoflurane anesthesia. Results c‐Fos straining showed that both aTRN PV and aTRN SST neurons are activated during the LOC period of propofol and isoflurane anesthesia. Optogenetic activation of aTRN PV and aTRN SST neurons promoted isoflurane induction and delayed the recovery of consciousness (ROC) after propofol and isoflurane anesthesia, meanwhile chemogenetic activation of the aTRN PV neurons displayed the similar effects. Moreover, optogenetic and chemogenetic activation of the aTRN neurons resulted in the accumulated burst suppression ratio (BSR) during propofol and isoflurane GA, although they represented different effects on the power distribution of EEG frequency. Conclusion Our findings reveal that the aTRN GABAergic neurons play a critical role in promoting the induction of propofol‐ and isoflurane‐mediated GA.