A Neural Circuit For Bergamot Essential Oil-Induced Anxiolytic Effects

Aromatic essential oils have been shown to relieve anxiety and enhance relaxation, although the neural circuits underlying these effects have remained unknown. Here, it is found that treatment with 1.0% bergamot essential oil (BEO) exerts anxiolytic-like effects through a neural circuit projecting from the anterior olfactory nucleus (AON) to the anterior cingulate cortex (ACC) in acute restraint stress model mice. Collectively, in vivo two-photon calcium imaging, viral tracing, and whole-cell patch clamp recordings show that inhalation exposure to 1.0% BEO can activate glutamatergic projections from the AON to GABAergic neurons in the ACC, which drives inhibition of local glutamatergic neurons (AON^Glu→ACC^GABA→Glu). Optogenetic or chemogenetic manipulation of this pathway can recapitulate or abolish the BEO-induced anxiolytic-like behavioral effects in mice with ARS. Beyond depicting a previously unrecognized pathway involved in stress response, this study provides a circuit mechanism for the effects of BEO and suggests a potential target for anxiety treatment.