Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents

Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from non-specific effects of structural damage. Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscilla-tion power in limbic areas and induced depression-like behaviors in rodents. Enhancing transmission of gamma oscillations from olfactory bulb to limbic structures by closed-loop electrical neuromodulation alle-viated these behaviors. By contrast, silencing gamma transmission by anti-phase closed-loop stimulation strengthened depression-like behaviors in naive animals. These induced behaviors were neutralized by ke-tamine treatment that restored limbic gamma power. Taken together, our results reveal a causal link between limbic gamma oscillations and depression-like behaviors in rodents. Interfering with these endogenous rhythms can affect behaviors in rodent models of depression, suggesting that restoring gamma oscillations may alleviate depressive symptoms.

Automated summary

By studying the effects of manipulating the olfactory bulb and its cortex efferents, researchers found that reducing gamma oscillations in the limbic areas of the brain can induce depression-like behaviors in rodents. However, enhancing gamma oscillations can alleviate these behaviors. The findings suggest that restoring gamma oscillations may be a potential treatment for depressive symptoms.