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

Abstract

While the mechanism of general anesthesia has been extensively studied, the underlying neural circuitry has yet to be fully understood. The parabrachial nucleus (PBN) plays a crucial role in modulating wakefulness and promoting arousal from general anesthesia. However, the specific role of PBN projections in the process of general anesthesia remains unclear. In this study, we bilaterally injected AAV-associated viruses encoding excitatory or inhibitory optogenetic probes into the PBN and implanted optical fibers in the LH or BF area. After four weeks, we optogenetically activated or inhibited the PBN-LH and PBN-BF pathways under 1.5 vol% isoflurane. We calculated the time it took for anesthesia induction and emergence, simultaneously monitoring changes in the burst-suppression ratio using electroencephalogram recording. Our findings indicate that optogenetic activation of the PBN-LH and PBN-BF projections plays a significant role in promoting both cortical and behavioral emergence from isoflurane inhalation, without significantly affecting the induction time. Conversely, photoinhibition of these pathways prolonged the recovery time, with no notable difference observed during the induction phase.In summary, our results demonstrate that the PBN-LH and PBN-BF pathways are crucial for promoting arousal from isoflurane general anesthesia, but do not have a pronounced impact on the induction phase.

Keywords: Isoflurane; Mechanism of anesthesia; Optogenetics; PBN-BF; PBN-LH.