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 th...

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Published in:Neuron (Cambridge, Mass.) Mass.), 2023-07, Vol.111 (13), p.2065-2075.e5
Main Authors: Li, Qun, Takeuchi, Yuichi, Wang, Jiale, Gellért, Levente, Barcsai, Livia, Pedraza, Lizeth K., Nagy, Anett J., Kozák, Gábor, Nakai, Shinya, Kato, Shigeki, Kobayashi, Kazuto, Ohsawa, Masahiro, Horváth, Gyöngyi, Kékesi, Gabriella, Lőrincz, Magor L., Devinsky, Orrin, Buzsáki, György, Berényi, Antal
Format: Article
Language:English
Subjects:
closed loop
depression
electrical stimulation
gamma oscillation
miniSOG
OBx
olfactory bulb
optogenetics
rat
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Summary: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 oscillation 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 alleviated 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 ketamine 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. •Suppression of OB or OB-PirC pathway decreases gamma and induces depressive symptoms•Anti-phase closed-loop stimulation of PirC gamma resembles depressive symptoms•Ketamine improves depressive symptoms induced by anti-phase gamma stimulation•In-phase gamma stimulation alleviated symptoms induced by LPS Li et al. report a causal link between limbic gamma oscillations and depression-like behaviors in rats. Interfering with the endogenous rhythms can affect mood-related behaviors in rat models of depression, suggesting that restoring gamma oscillations may improve depressive symptoms.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2023.04.013