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Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus

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  • Loredana Cumpana

    (Ecole Polytechnique Fédérale de Lausanne
    Ecole Polytechnique Fédérale de Lausanne)

  • Olivia Zanoletti

    (Ecole Polytechnique Fédérale de Lausanne
    Ecole Polytechnique Fédérale de Lausanne)

  • Dinesh Kankanamge

    (Washington University School of Medicine)

  • Bryan Copits

    (Washington University School of Medicine)

  • Carmen Sandi

    (Ecole Polytechnique Fédérale de Lausanne
    Ecole Polytechnique Fédérale de Lausanne)

  • Simone Astori

    (Ecole Polytechnique Fédérale de Lausanne
    Ecole Polytechnique Fédérale de Lausanne)

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.

Suggested Citation

  • Loredana Cumpana & Olivia Zanoletti & Dinesh Kankanamge & Bryan Copits & Carmen Sandi & Simone Astori, 2025. "Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63118-6
    DOI: 10.1038/s41467-025-63118-6
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    References listed on IDEAS

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    1. Amanda L. Schott & Justin Baik & Shinjae Chung & Franz Weber, 2023. "A medullary hub for controlling REM sleep and pontine waves," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Mojtaba Bandarabadi & Carolina Gutierrez Herrera & Thomas C. Gent & Claudio Bassetti & Kaspar Schindler & Antoine R. Adamantidis, 2020. "A role for spindles in the onset of rapid eye movement sleep," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Ze Zhang & Corinne Beier & Tenley Weil & Samer Hattar, 2021. "The retinal ipRGC-preoptic circuit mediates the acute effect of light on sleep," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Matthew T. Birnie & Annabel K. Short & Gregory B. Carvalho & Lara Taniguchi & Benjamin G. Gunn & Aidan L. Pham & Christy A. Itoga & Xiangmin Xu & Lulu Y. Chen & Stephen V. Mahler & Yuncai Chen & Talli, 2023. "Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
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