0042 EEP-PROMOTING GABAERGIC NEURONS IN THE PARAFACIAL ZONE PLAY A ROLE IN ANESTHETIC-INDUCED UNCONSCIOUSNESS IN MICE

Abstract Introduction Although the precise mechanisms by which anesthetics induce unconsciousness are unknown, there is evidence that shared brain circuits engaged during sleep and general anesthesia. The parafacial zone (PZ) of brainstem has recently been identified as a sleep-promoting region. Specifically, GABAergic neurons in PZ (PZ-GABA) active non-REM sleep. role PZ-GABA anesthetic-induced hypnosis unknown. We hypothesized anesthesia contribute to hypnosis. Methods Adult C57BL6 mice (n = 3) were subjected two-hour exposures hypnotic dose an inhaled anesthetic (isoflurane 1.2%) oxygen, non-immobilizer, F6, lacks properties (1,2-dicholorohexafluorocyclobutane 3%) or oxygen alone. brains harvested immediately following these exposures. sections immunostained for c-Fos GAD. To study isoflurane-induced hypnosis, ablation was performed adult bitransgenic Vgat-ires-Cre;Ai6 express fluorescent reporter 5 per group). Anesthesia sensitivity evaluated weekly four weeks after virus injections assessing presence righting reflex Results In PZ, Isoflurane selectively activated GAD-positive compared treated with F6 oxygen. (P < 0.01 both vs. Isoflurane, one-way ANOVA) Furthermore, lacking demonstrated resistance induction, decreased maintenance phase, consistently increased propensity emerge from (For induction emergence, upper 95% CI EC50 at baseline lower than all time points injections. For P 0.05 1-week, Conclusion isoflurane exposure. Moreover, absence resulted These findings suggest PZ-GABA, region brainstem, plays important Support (if any) NIH (T32HL7713-27, T32 NS091006), ATS-ASPIRE