General Anesthesia Activates a Central Anxiolytic Center in the BNST

Abstract

SUMMARYLow 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 (ovBNSTGA). A majority of ovBNSTGAneurons express neurotensin receptor 1 (Ntsr1) and innervate brain regions known to regulate anxiety and stress responses. Optogenetic activation ovBNSTGAor ovBNSTNtsr1neurons 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 ovBNSTGA/ovBNSTNtsr1neurons as one of the brain’s endogenous anxiolytic centers and a potential therapeutic target for treating anxiety-related disorders.HIGHLIGHTSGeneral anesthetics and anxiolytics activate a population of neurons in the ovBNSTAnesthesia-activated ovBNST neurons bidirectionally modulate anxiety-like behaviorMost anesthesia-activated ovBNST neurons express neurotensin receptor 1ovBNSTNtsr1neuron activation shifts autonomic responses to an anxiolytic state