Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice
Abstract 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42662-z |
| _version_ | 1827781169017520128 |
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| author | Yun-Feng Zhang Jialiang Wu Yingqi Wang Natalie L. Johnson Janardhan P. Bhattarai Guanqing Li Wenqiang Wang Camilo Guevara Hannah Shoenhard Marc V. Fuccillo Daniel W. Wesson Minghong Ma |
| author_facet | Yun-Feng Zhang Jialiang Wu Yingqi Wang Natalie L. Johnson Janardhan P. Bhattarai Guanqing Li Wenqiang Wang Camilo Guevara Hannah Shoenhard Marc V. Fuccillo Daniel W. Wesson Minghong Ma |
| author_sort | Yun-Feng Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-11T15:14:03Z |
| format | Article |
| id | doaj.art-b3431fd88a3540e0906c1897b6e26823 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T15:14:03Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b3431fd88a3540e0906c1897b6e268232023-10-29T12:28:56ZengNature PortfolioNature Communications2041-17232023-10-0114111710.1038/s41467-023-42662-zVentral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in miceYun-Feng Zhang0Jialiang Wu1Yingqi Wang2Natalie L. Johnson3Janardhan P. Bhattarai4Guanqing Li5Wenqiang Wang6Camilo Guevara7Hannah Shoenhard8Marc V. Fuccillo9Daniel W. Wesson10Minghong Ma11State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesDepartment of Neuroscience, University of Pennsylvania Perelman School of MedicineDepartment of Pharmacology and Therapeutics, University of FloridaDepartment of Neuroscience, University of Pennsylvania Perelman School of MedicineState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesDepartment of Neuroscience, University of Pennsylvania Perelman School of MedicineDepartment of Neuroscience, University of Pennsylvania Perelman School of MedicineDepartment of Neuroscience, University of Pennsylvania Perelman School of MedicineDepartment of Pharmacology and Therapeutics, University of FloridaDepartment of Neuroscience, University of Pennsylvania Perelman School of MedicineAbstract 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.https://doi.org/10.1038/s41467-023-42662-z |
| spellingShingle | Yun-Feng Zhang Jialiang Wu Yingqi Wang Natalie L. Johnson Janardhan P. Bhattarai Guanqing Li Wenqiang Wang Camilo Guevara Hannah Shoenhard Marc V. Fuccillo Daniel W. Wesson Minghong Ma Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice Nature Communications |
| title | Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice |
| title_full | Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice |
| title_fullStr | Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice |
| title_full_unstemmed | Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice |
| title_short | Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice |
| title_sort | ventral striatal islands of calleja neurons bidirectionally mediate depression like behaviors in mice |
| url | https://doi.org/10.1038/s41467-023-42662-z |
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