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

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, Lorincz, Magor L., Devinsky, Orrin, Buzsáki, György and Berényi, Antal 2023. Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents. Neuron 111 (13) , pp. 2065-2075. 10.1016/j.neuron.2023.04.013

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0896-6273
Date of First Compliant Deposit:	17 April 2024
Date of Acceptance:	12 April 2023
Last Modified:	17 Apr 2024 15:41
URI:	https://orca.cardiff.ac.uk/id/eprint/167967

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