State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, 100101, Beijing, China.
Nat Commun. 2023 Oct 28;14(1):6887. doi: 10.1038/s41467-023-42662-z.
The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells, predominantly in the olfactory tubercle (OT). These OT D3 neurons regulate self-grooming, a repetitive behavior manifested in affective disorders. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a crucial role of OT D3 neurons in bidirectionally mediating depression-like behaviors, suggesting a potential therapeutic target.
腹侧纹状体是一种与抑郁症病理生理学相关的奖励中心。它包含卡列哈岛，即多巴胺 D3 受体表达的颗粒细胞簇，主要位于嗅结节（OT）。这些 OT D3 神经元调节自我梳理，这是一种在情感障碍中表现出来的重复性行为。在这里，我们表明慢性束缚应激（CRS）可诱导小鼠产生强烈的抑郁样行为，并降低 OT D3 神经元的兴奋性。这些神经元的消融或抑制会导致抑郁样行为，而其激活则可改善 CRS 诱导的抑郁样行为。此外，OT D3 神经元的激活具有奖赏作用，而当梳理被阻断时，这种作用会减弱。最后，我们提出了一个模型，解释了 OT D3 神经元如何通过与投射到中脑多巴胺神经元的 OT 棘突投射神经元（SPN）的突触连接来影响多巴胺的释放。我们的研究揭示了 OT D3 神经元在双向调节抑郁样行为中的关键作用，提示其可能成为一种潜在的治疗靶点。
