Scents have been employed for millennia to allay fear and stress, but whether they do so is poorly understood. In response to fear and stress, hypothalamic corticotropin releasing hormone neurons (CRHNs) induce increases in blood stress hormones. Here, we find that certain structurally and perceptually dissimilar odorants can block mouse stress hormone responses to three potent stressors: physical restraint, predator odor, and male-male social confrontation. Both odorants activate GABAergic inhibitory neurons presynaptic to CRHNs in the hypothalamic ventromedial nucleus (VMH). Stimulation of those neurons inhibits restraint-induced activation of CRHNs and stress hormone increase, mimicking a blocking odorant. Conversely, their silencing prevents odorant blocking of both responses. Notably, we also observed odor blocking of stressor activation in neurons presynaptic to CRHNs in the bed nucleus of the stria terminalis (BNST). Together, these findings indicate that selected odorants can indeed block stress responses, and that odor blocking can occur via two routes: a direct route in which blocking odor signals directly inhibit CRHNs and an indirect route in which they inhibit stressor activation of neurons presynaptic to CRHNs and prevent them from transmitting stress signals to CRHNs.
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