Anatomical substrates of Rapid Eye Movement sleep rebound in a rodent model of post-sevoflurane sleep disruption

Abstract

Background Previous research suggests that sevoflurane anesthesia may prevent the brain from accessing REM sleep. If true, then patterns of neural activity observed in REM-on and REM-off neuronal populations during recovery from sevoflurane should resemble those seen after REM sleep deprivation. In this study we hypothesized that, relative to controls, animals exposed to sevoflurane present with a distinct expression pattern of c-Fos, a marker of neuronal activation, in a cluster of nuclei classically associated with REM sleep, and that such expression in sevoflurane -exposed and REM sleep-deprived animals is largely similar. Methods Adult rats and Targeted Recombination in Active Populations mice were implanted with electroencephalographic electrodes for sleep-wake recording and randomized to sevoflurane, REM deprivation or control conditions. Conventional c-Fos immunohistochemistry and genetically-tagged c-Fos labeling were used to quantify activated neurons in a group of REM-associated nuclei in the midbrain and basal forebrain. Results REM sleep duration increased during recovery from sevoflurane anesthesia relative to controls (157.0 ± 24.8 min vs 124.2 ± 27.8 min, P=0.003), and temporally correlated with increased c-Fos expression in the sublaterodorsal nucleus (SLD), a region active during REM sleep (176.0 ± 36.6 cells vs 58.8 ± 8.7, P=0.014), and decreased c-Fos expression in the ventrolateral periaqueductal gray (vlPAG), a region that is inactive during REM sleep (34.8 ± 5.3 cells vs 136.2 ± 19.6, P=0.001). Fos changes similar to those seen in sevoflurane-exposed mice were observed in REM-deprived animals, relative to controls (SLD: 85.0 ± 15.5 cells vs 23.0 ± 1.2, P=0.004; vlPAG: 652.8 ± 71.7 cells vs 889.3 ± 66.8, P=0.042). Conclusions In rodents recovering from sevoflurane, REM-on and REM-off neuronal activity maps closely resemble those of REM sleep-deprived animals. These findings provide new evidence in support of the idea that sevoflurane does not substitute for endogenous REM sleep.