The neural ensembles activated by propofol and isoflurane anesthesia across the whole mouse brain

General anesthesia has been widely used in surgical procedures. Propofol and isoflurane are the most commonly used injectable and inhaled anesthetics, respectively. The various adverse effects induced by propofol and isoflurane are highly associated with the anesthetic-dependent change of brain activities. In this work, we aim to delineate a brain-wide neuronal activity landscape of injectable versus inhaled anesthetics to understand the neural basis underlying the different physiological effects induced by these two major types of anesthetics. Through detailed scanning of the whole mouse brain subjected to propofol or isoflurane anesthesia, in total, we identified 17 subcortical regions, 3 of which (anterodorsal preoptic nucleus, ADP; lateral habenular, LHb; inferior olivary nucleus, ION) were specifically activated by propofol, and 3 (ventral part of the lateral septum, LSV; the intermediate part of the lateral septum, LSI; the solitary tract nucleus, Sol) were specifically activated by isoflurane, with the remaining 11 were activated by both two anesthetics. Moreover, within the 17 brain regions, ADP, SubCV (subcoeruleus nucleus, ventral part), PCRtA (parvicellular reticular nucleus, alpba part) and ION were newly identified that activated by propofol or isoflurane, respectively. By using Targeted Recombination in Active Populations (TRAP) technique, we further showed that propofol and isoflurane largely activate the same group of neurons in supraoptic nucleus (SON), but activate different groups of neurons in central amygdala (CeA). Our results reveals the neural ensembles activated by injectable and inhaled anesthetics, and provides detailed anatomical references for future studies on general anesthesia.