Journal
MOLECULAR NEUROBIOLOGY
Volume 58, Issue 11, Pages 5635-5648Publisher
SPRINGER
DOI: 10.1007/s12035-021-02522-7
Keywords
Depression; Hypolocomotion; VTA; SNr; Dopaminergic projection
Categories
Funding
- National Natural Science Foundation of China [31871073, 31571044, 31600821]
- Program for New Century Excellent Talents in University [NCET-10-0415]
- Fundamental Research Funds for the Central Universities [HUST: 2019kfyXJJS081]
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The study found that chronic social defeat stress (CSDS) can affect the spontaneous locomotor activity of mice, but not their grip strength and forced locomotion ability.
Numerous human clinical studies have suggested that decreased locomotor activity is a common symptom of major depressive disorder (MDD), as well as other psychiatric diseases. In MDD, the midbrain ventral tegmental area (VTA) dopamine (DA) neurons are closely related to regulate the information processing of reward, motivation, cognition, and aversion. However, the neural circuit mechanism that underlie the relationship between VTA-DA neurons and MDD-related motor impairments, especially hypolocomotion, is still largely unknown. Herein, we investigate how the VTA-DA neurons contribute to the hypolocomotion performance in chronic social defeat stress (CSDS), a mouse model of depression-relevant neurobehavioral states. The results show that CSDS could affect the spontaneous locomotor activity of mice, but not the grip strength and forced locomotor ability. Chemogenetic activation of VTA-DA neurons alleviated CSDS-induced hypolocomotion. Subsequently, quantitative whole-brain mapping revealed decreased projections from VTA-DA neurons to substantia nigra pars reticulata (SNr) after CSDS treatment. Optogenetic activation of dopaminergic projection from VTA to SNr with the stimulation of phasic firing, but not tonic firing, could significantly increase the locomotor activity of mice. Moreover, chemogenetic activation of VTA-SNr dopaminergic circuit in CSDS mice could also rescued the decline of locomotor activity. Taken together, our data suggest that the VTA-SNr dopaminergic projection mediates CSDS-induced hypolocomotion, which provides a theoretical basis and potential therapeutic target for MDD.
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