Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration
Orexin signaling in the ventral tegmental area and substantia nigra promotes locomotion and reward processing, but it is not clear whether dopaminergic neurons directly mediate these effects. We show that dopaminergic neurons in these areas mainly express orexin receptor subtype 1 (Ox1R). In contras...
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/91716 |
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| author | Xing Xiao Gagik Yeghiazaryan Fynn Eggersmann Anna Lena Cremer Heiko Backes Peter Kloppenburg Anne Christine Hausen |
| author_facet | Xing Xiao Gagik Yeghiazaryan Fynn Eggersmann Anna Lena Cremer Heiko Backes Peter Kloppenburg Anne Christine Hausen |
| author_sort | Xing Xiao |
| collection | DOAJ |
| description | Orexin signaling in the ventral tegmental area and substantia nigra promotes locomotion and reward processing, but it is not clear whether dopaminergic neurons directly mediate these effects. We show that dopaminergic neurons in these areas mainly express orexin receptor subtype 1 (Ox1R). In contrast, only a minor population in the medial ventral tegmental area express orexin receptor subtype 2 (Ox2R). To analyze the functional role of Ox1R signaling in dopaminergic neurons, we deleted Ox1R specifically in dopamine transporter-expressing neurons of mice and investigated the functional consequences. Deletion of Ox1R increased locomotor activity and exploration during exposure to novel environments or when intracerebroventricularely injected with orexin A. Spontaneous activity in home cages, anxiety, reward processing, and energy metabolism did not change. Positron emission tomography imaging revealed that Ox1R signaling in dopaminergic neurons affected distinct neural circuits depending on the stimulation mode. In line with an increase of neural activity in the lateral paragigantocellular nucleus (LPGi) of Ox1RΔDAT mice, we found that dopaminergic projections innervate the LPGi in regions where the inhibitory dopamine receptor subtype D2 but not the excitatory D1 subtype resides. These data suggest a crucial regulatory role of Ox1R signaling in dopaminergic neurons in novelty-induced locomotion and exploration. |
| format | Article |
| id | doaj-art-8497747eecf54e55a72a554af8bdf541 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-8497747eecf54e55a72a554af8bdf5412025-01-22T14:19:19ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011210.7554/eLife.91716Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and explorationXing Xiao0https://orcid.org/0000-0003-3590-7430Gagik Yeghiazaryan1Fynn Eggersmann2Anna Lena Cremer3Heiko Backes4Peter Kloppenburg5https://orcid.org/0000-0002-4554-404XAnne Christine Hausen6Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, GermanyDepartment of Biology, Institute for Zoology, University of Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, GermanyDepartment of Biology, Institute for Zoology, University of Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, GermanyMax Planck Institute for Metabolism Research, Multimodal Imaging of Brain Metabolism Group, Cologne, GermanyMax Planck Institute for Metabolism Research, Multimodal Imaging of Brain Metabolism Group, Cologne, GermanyDepartment of Biology, Institute for Zoology, University of Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, GermanyMax Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, GermanyOrexin signaling in the ventral tegmental area and substantia nigra promotes locomotion and reward processing, but it is not clear whether dopaminergic neurons directly mediate these effects. We show that dopaminergic neurons in these areas mainly express orexin receptor subtype 1 (Ox1R). In contrast, only a minor population in the medial ventral tegmental area express orexin receptor subtype 2 (Ox2R). To analyze the functional role of Ox1R signaling in dopaminergic neurons, we deleted Ox1R specifically in dopamine transporter-expressing neurons of mice and investigated the functional consequences. Deletion of Ox1R increased locomotor activity and exploration during exposure to novel environments or when intracerebroventricularely injected with orexin A. Spontaneous activity in home cages, anxiety, reward processing, and energy metabolism did not change. Positron emission tomography imaging revealed that Ox1R signaling in dopaminergic neurons affected distinct neural circuits depending on the stimulation mode. In line with an increase of neural activity in the lateral paragigantocellular nucleus (LPGi) of Ox1RΔDAT mice, we found that dopaminergic projections innervate the LPGi in regions where the inhibitory dopamine receptor subtype D2 but not the excitatory D1 subtype resides. These data suggest a crucial regulatory role of Ox1R signaling in dopaminergic neurons in novelty-induced locomotion and exploration.https://elifesciences.org/articles/91716orexindopaminecontext-induced locomotion |
| spellingShingle | Xing Xiao Gagik Yeghiazaryan Fynn Eggersmann Anna Lena Cremer Heiko Backes Peter Kloppenburg Anne Christine Hausen Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration eLife orexin dopamine context-induced locomotion |
| title | Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration |
| title_full | Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration |
| title_fullStr | Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration |
| title_full_unstemmed | Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration |
| title_short | Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration |
| title_sort | deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty induced locomotion and exploration |
| topic | orexin dopamine context-induced locomotion |
| url | https://elifesciences.org/articles/91716 |
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