Selective optogenetic modulation of the PBN terminals in the lateral hypothalamic area and basal forebrain regulates emergence from isoflurane anesthesia in mice

Although the mechanism of general anesthesia has been extensively studied, the underlying neural circuitry remains to be fully elucidated. The parabrachial nucleus (PBN) is vital for modulating wakefulness and promoting arousal from general anesthesia. However, it remains unclear that the role of the PBN projections in the process of general anesthesia. Bilaterally injecting AAV associated viruses encoding excitatory or inhibitory optogenetic probes into the PBN, and then implanting the optical fibers in the LH or BF area bilaterally. After four weeks, the two PBN-LH and PBN-BF pathways were optogenetically activated or inhibited under 1.5 vol% isoflurane. The time of induction of and emergence from anesthesia was calculated. Burst-suppression ratio changes were determined simultaneously using electroencephalogram recording. We found that optogenetic activation of the PBN-LH and PBN-BF projections was involved in promoting both the cortical and behavioral emergence from isoflurane inhalation but had no significant impact on the induction time. Furthermore, photoinhibition of the two pathways prolonged the recovery time and there was also no apparent difference during the induction stage. Therefore, our results demonstrated that the PBN-LH and PBN-BF pathways are crucial for promoting arousal from isoflurane general anesthesia, but have no obvious effects on the induction phase.