Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus
Abstract Corticotropin-releasing hormone (CRH) is a peptide associated with stress and anxiety that acts as a potent modulator throughout the nervous system. The thalamic reticular nucleus (TRN) displays high expression of the CRH receptor 1 (CRHR1), but whether CRH modulates key TRN functions, such...
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| Format: | Article |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-63118-6 |
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| author | Loredana Cumpana Olivia Zanoletti Dinesh Kankanamge Bryan Copits Carmen Sandi Simone Astori |
| author_facet | Loredana Cumpana Olivia Zanoletti Dinesh Kankanamge Bryan Copits Carmen Sandi Simone Astori |
| author_sort | Loredana Cumpana |
| collection | DOAJ |
| description | Abstract Corticotropin-releasing hormone (CRH) is a peptide associated with stress and anxiety that acts as a potent modulator throughout the nervous system. The thalamic reticular nucleus (TRN) displays high expression of the CRH receptor 1 (CRHR1), but whether CRH modulates key TRN functions, such as sleep spindle rhythmogenesis, remained unexplored. Combining polysomnographic and photometric recordings in mice, we show that CRH release in TRN during non-rapid-eye movement sleep (NREMS) oscillates with a ~50-s periodicity, anti-correlating with sleep spindle dynamics. Optogenetic manipulations of CRH release in TRN modulated NREMS fragmentation through microarousals with corresponding changes in sigma and delta power. In ex-vivo recordings, CRHR1 activation decreased the propensity of TRN neurons to fire calcium bursts. CRHR1 knockdown in parvalbumin TRN neurons prevented the effects of CRH on NREMS and TRN bursting. Thus, CRHR1 impacts NREMS by modulating thalamic excitability, providing a potential target to stabilize sleep impairments associated with stress and anxiety. |
| format | Article |
| id | doaj-art-bc4838f9ed5345ffb080616021d459eb |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bc4838f9ed5345ffb080616021d459eb2025-08-24T11:38:30ZengNature PortfolioNature Communications2041-17232025-08-0116111810.1038/s41467-025-63118-6Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleusLoredana Cumpana0Olivia Zanoletti1Dinesh Kankanamge2Bryan Copits3Carmen Sandi4Simone Astori5Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneLaboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineLaboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneLaboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de LausanneAbstract Corticotropin-releasing hormone (CRH) is a peptide associated with stress and anxiety that acts as a potent modulator throughout the nervous system. The thalamic reticular nucleus (TRN) displays high expression of the CRH receptor 1 (CRHR1), but whether CRH modulates key TRN functions, such as sleep spindle rhythmogenesis, remained unexplored. Combining polysomnographic and photometric recordings in mice, we show that CRH release in TRN during non-rapid-eye movement sleep (NREMS) oscillates with a ~50-s periodicity, anti-correlating with sleep spindle dynamics. Optogenetic manipulations of CRH release in TRN modulated NREMS fragmentation through microarousals with corresponding changes in sigma and delta power. In ex-vivo recordings, CRHR1 activation decreased the propensity of TRN neurons to fire calcium bursts. CRHR1 knockdown in parvalbumin TRN neurons prevented the effects of CRH on NREMS and TRN bursting. Thus, CRHR1 impacts NREMS by modulating thalamic excitability, providing a potential target to stabilize sleep impairments associated with stress and anxiety.https://doi.org/10.1038/s41467-025-63118-6 |
| spellingShingle | Loredana Cumpana Olivia Zanoletti Dinesh Kankanamge Bryan Copits Carmen Sandi Simone Astori Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus Nature Communications |
| title | Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus |
| title_full | Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus |
| title_fullStr | Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus |
| title_full_unstemmed | Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus |
| title_short | Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus |
| title_sort | corticotropin releasing hormone modulates nrem sleep consolidation through the thalamic reticular nucleus |
| url | https://doi.org/10.1038/s41467-025-63118-6 |
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