Abstract
Rationale
Major depression is a serious, but common, psychological disorder, which consists of a long-lasting depressive mood, feelings of helplessness, anhedonia, and sleep disturbances. It has been reported that rats with bilateral olfactory bulbectomies (OBXs) exhibit depressive-like behaviors which indicates that the olfactory bulb (OB) plays an important role in the formation of depression. However, which type of OB neurons plays an important role in the formation of depression remains unclear.
Objective
To determine the role of OB neuronal types in depression and related sleep-wake dysfunction.
Methods
Firstly, we established and evaluated a conventional physical bilateral OBX depression model. Secondly, we used chemical methods to ablate OB neurons, while maintaining the original shape, and evaluated depressive-like behaviors. Thirdly, we utilized AAV-flex-taCasp3-TEVp and transgenetic mice to specifically ablate the OB GABAergic or glutamatergic neurons, then evaluated depressive-like behaviors.
Results
Compared with measured parameters in sham mice, mice with OBXs or ibotenic acid–induced OB lesions exhibited depressive-like behaviors and sleep disturbances, as demonstrated by results of depressive-like behavior tests and sleep recordings. Selective lesioning of OB glutamatergic neurons, but not GABAergic neurons induced depressive-like behaviors and increased rapid eye movement sleep during the light phase of the circadian cycle.
Conclusions
These results indicate that OB glutamatergic neurons play a key role in olfactory-related depression and sleep disturbance.
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Acknowledgments
We thank Professor Zhen-Gang Yang (Institutes of Brain Science, Fudan University) for kindly providing the probes to target mRNA molecules.
Funding
This study was financially supported in part by grants-in-aid for scientific research from the National Natural Science Foundation of China (31530035, 31671099, 31871072, 31571103, and 81701305), Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and ZJLab, and Program for Shanghai Outstanding Academic Leaders (to Zhi-Li Huang).
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Rui-Xi Li, Zhi-Li Huang, and Wei-Min Qu provided substantial contributions to the conception and design of the work and modified the manuscript. Hui Dong provided instruction and good suggestion. Mao-Yun Yuan and Ze-ka Chen performed the acquisition and analysis of data for the work and wrote the original draft. Tian-Xiao Wang, Jian Ni, and Shi-Yu Jiang were involved in the experiments. All authors have read the paper and agreed to be authors on the paper.
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All experimental procedures involving animals were approved by the Animal Experiment and Use Committee at the Shanghai Medical School of Fudan University (Permit No. 20140226-024).
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The authors declare that they have no conflicts of interest.
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Yuan, MY., Chen, ZK., Ni, J. et al. Ablation of olfactory bulb glutamatergic neurons induces depressive-like behaviors and sleep disturbances in mice. Psychopharmacology 237, 2517–2530 (2020). https://doi.org/10.1007/s00213-020-05552-6
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DOI: https://doi.org/10.1007/s00213-020-05552-6