The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons
Abstract Though circadian locomotor rhythms are primarily driven by the suprachiasmatic nucleus, voluntary motor behavior also requires dopaminergic neuron (DAN) activity. However, it is unknown whether DAN molecular and electrophysiological properties and rhythmic motor behaviors are dependent on a...
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Nature Portfolio
2025-07-01
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| Series: | npj Biological Timing and Sleep |
| Online Access: | https://doi.org/10.1038/s44323-025-00044-2 |
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| author | Ananya Swaroop Jodi R. Paul Laura J. McMeekin Ashley M. Barnett Alana M. Colafrancesco Drèson L. Russell Camille M. Smith Micah S. Simmons Laura A. Volpicelli-Daley Rita M. Cowell Karen L. Gamble |
| author_facet | Ananya Swaroop Jodi R. Paul Laura J. McMeekin Ashley M. Barnett Alana M. Colafrancesco Drèson L. Russell Camille M. Smith Micah S. Simmons Laura A. Volpicelli-Daley Rita M. Cowell Karen L. Gamble |
| author_sort | Ananya Swaroop |
| collection | DOAJ |
| description | Abstract Though circadian locomotor rhythms are primarily driven by the suprachiasmatic nucleus, voluntary motor behavior also requires dopaminergic neuron (DAN) activity. However, it is unknown whether DAN molecular and electrophysiological properties and rhythmic motor behaviors are dependent on a molecular clock. Here, we show substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) DANs rhythmically express clock genes, and conditional deletion of Bmal1 in DANs reduces motivated locomotion without robust cell loss or gross motor impairment. Further, DAN Bmal1 conditional deletion disrupts 24-h rhythms in spike rate, revealing ultradian rhythms (~4–8 h). Lastly, SNc DAN bursting varies across time of day and increased early night bursting is dependent on the molecular clock and L-type calcium channel activation. Collectively, we provide evidence of a cell-intrinsic dopaminergic clock which regulates key behaviors and physiology. Future studies should consider the contribution of disrupted DAN molecular clocks in age-related motor diseases like Parkinson’s Disease. |
| format | Article |
| id | doaj-art-41cd59e0c056447d8aa19407914cb42e |
| institution | DOAJ |
| issn | 2948-281X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biological Timing and Sleep |
| spelling | doaj-art-41cd59e0c056447d8aa19407914cb42e2025-08-20T03:03:44ZengNature Portfolionpj Biological Timing and Sleep2948-281X2025-07-012111310.1038/s44323-025-00044-2The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neuronsAnanya Swaroop0Jodi R. Paul1Laura J. McMeekin2Ashley M. Barnett3Alana M. Colafrancesco4Drèson L. Russell5Camille M. Smith6Micah S. Simmons7Laura A. Volpicelli-Daley8Rita M. Cowell9Karen L. Gamble10Department of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Neuroscience, Southern ResearchDepartment of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Neurology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Neurology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Neurology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Neurology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at BirminghamAbstract Though circadian locomotor rhythms are primarily driven by the suprachiasmatic nucleus, voluntary motor behavior also requires dopaminergic neuron (DAN) activity. However, it is unknown whether DAN molecular and electrophysiological properties and rhythmic motor behaviors are dependent on a molecular clock. Here, we show substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) DANs rhythmically express clock genes, and conditional deletion of Bmal1 in DANs reduces motivated locomotion without robust cell loss or gross motor impairment. Further, DAN Bmal1 conditional deletion disrupts 24-h rhythms in spike rate, revealing ultradian rhythms (~4–8 h). Lastly, SNc DAN bursting varies across time of day and increased early night bursting is dependent on the molecular clock and L-type calcium channel activation. Collectively, we provide evidence of a cell-intrinsic dopaminergic clock which regulates key behaviors and physiology. Future studies should consider the contribution of disrupted DAN molecular clocks in age-related motor diseases like Parkinson’s Disease.https://doi.org/10.1038/s44323-025-00044-2 |
| spellingShingle | Ananya Swaroop Jodi R. Paul Laura J. McMeekin Ashley M. Barnett Alana M. Colafrancesco Drèson L. Russell Camille M. Smith Micah S. Simmons Laura A. Volpicelli-Daley Rita M. Cowell Karen L. Gamble The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons npj Biological Timing and Sleep |
| title | The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons |
| title_full | The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons |
| title_fullStr | The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons |
| title_full_unstemmed | The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons |
| title_short | The molecular clock drives motivated locomotion and time-of-day-dependent firing patterns in mouse dopaminergic neurons |
| title_sort | molecular clock drives motivated locomotion and time of day dependent firing patterns in mouse dopaminergic neurons |
| url | https://doi.org/10.1038/s44323-025-00044-2 |
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