General Anesthesia Activates a Central Anxiolytic Center in the BNST

SUMMARY Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects. How these different drugs exert these anxiolytic effects is not well understood. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that is activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNST GA ). A majority of ovBNST GA neurons express neurotensin receptor 1 (Ntsr1) and innervate brain regions known to regulate anxiety and stress responses. Optogenetic activation ovBNST GA or ovBNST Ntsr1 neurons significantly attenuated anxiety-like behaviors in both naïve animals and mice with inflammatory pain, while inhibition of these cells increased anxiety. Notably, activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety through modulation of the autonomic nervous system. Our study identifies ovBNST GA /ovBNST Ntsr1 neurons as one of the brain’s endogenous anxiolytic centers and a potential therapeutic target for treating anxiety-related disorders. HIGHLIGHTS General anesthetics and anxiolytics activate a population of neurons in the ovBNST Anesthesia-activated ovBNST neurons bidirectionally modulate anxiety-like behavior Most anesthesia-activated ovBNST neurons express neurotensin receptor 1 ovBNST Ntsr1 neuron activation shifts autonomic responses to an anxiolytic state