Neuroinflammation in Olfactory Circuits Underlies Odor Hypersensitivity in a Rodent Model of Depression

Depression can affect quality of life in several ways, including reduced concentration, motivation, and energy. Olfactory anhedonia in depressed patients results in a decreased attraction to pleasant smells and increased aversion to unpleasant odors. We used the Unpredictable Chronic Mild Stress (UCMS) as an induced-depression model to study olfactory perception and avoidance in mice of both sexes. After inducing a depression-like state, we observed an increased sensitivity to aversive odorants as well as an associated increase in escape behavior in an odorized environment. Previous studies using a similar model of induced depression have demonstrated increased neuroinflammation in brain areas, including the medial prefrontal cortex, but few have explored the effects in olfactory processing centers. We used immunohistochemistry to measure changes in astrocytic activation and microglia in multiple olfactory regions of the brain to further investigate the connection between neuroinflammation and odor hypersensitivity. We found an increase in the number of astrocytes in the medial amygdala, which receives direct input from the accessory olfactory bulb, and more complex microglial morphology in the olfactory bulb and piriform cortex. Additional analysis revealed a relationship between the extent of neuroinflammation and odor aversion. Our findings indicate that glial cells in sensory processing centers are sensitive to stress-induced depression and contribute to altered olfactory perception.