Glutamatergic neurons of piriform cortex delay induction of inhalational general anesthesia

Since their clinical application in the 1840s, the greatest mystery surrounding general anesthesia (GA) is how different kinds of general anesthetics cause reversible unconsciousness, and the precise neural mechanisms underlying the processes. Over past years, although many studies revealed the roles of cortex, thalamus, brainstem, especially the sleep-wake circuits in GA-induced loss of consciousness (LOC),the full picture of the neural circuit mechanism of GA is still largely unknown. Recent studies have focused on the importance of other brain regions. Here, we report that the activity of glutamatergic (Glu) neurons in the piriform cortex (PC), a critical brain region for odor encoding, began to increase during the LOC of GA and gradually recovered after recovery of consciousness. Chemical lesions of the anterior PC (APC) neurons accelerated the induction time of isoflurane anesthesia. Chemogenetic and optogenetic activation of APC^Glu neurons prolonged isoflurane and sevoflurane anesthesia induction, whereas APC^Glu neuron inhibition displayed the opposite effects. Moreover, the modification of APC^Glu neurons did not affect the induction or emergence time of propofol GA. In addition, odor processing may be partially involved in the induction of isoflurane and sevoflurane GA regulated by APC^Glu neurons. In conclusion, our findings reveal a critical role of APC^Glu neurons in inhalational GA induction.