General Anesthesia Activates an Anxiolytic Neuronal Group in the Bed Nucleus of the Stria Terminalis

Abstract

General anesthesia and anesthetics, in addition to the well-known properties of unconsciousness, amnesia, analgesia, and akinesia, also have anxiolytic properties. Albeit successfully used clinically to treat patients with various anxiety disorders, the common underlying mechanisms that these drugs and compounds rely on to attenuate anxiety largely remain unclear, partially due to the difficulties in investigating neuropsychological disorders in rodent models, and in comprehensively studying both behavioral and physiological aspects of anxiety. Using transgenic mouse models and a variety of histochemistry, behavioral, and physiological recording methods, we aimed to decipher the brain regions and circuit mechanisms of anesthesia-induced anxiolysis. We discovered a unique population of neurons in the mouse ovBNST to be commonly activated by multiple anesthetics and anxiolytics, to innervate brain regions critical for the regulation of emotional and autonomic responses to stressors, and to express peptides and markers previously known to be associated with anxiolysis. We further showed that optogenetic activation of these neurons could attenuate anxiety-like behaviors, while the inhibitions of these neurons had opposite behavioral effects. Lastly, we showed that optogenetic activation of these neurons led to changes in heart rate, heart rate variability, and other bodily reactions involved in stress management. Our study indicates ovBNST to be a potential therapeutic target for anxiolysis.