Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Communications Biology
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. communications biology
  3. articles
  4. article
Entrained cortical delta–spindle activity, not periodic synchrony, prevents arousal by NREM thalamic bursts
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 23 January 2026

Entrained cortical delta–spindle activity, not periodic synchrony, prevents arousal by NREM thalamic bursts

  • Xiaowei Liu  ORCID: orcid.org/0009-0006-8716-59251 na1,
  • Jing Guang  ORCID: orcid.org/0000-0002-5623-07161 na1,
  • Zvi Israel2,
  • Denise Wajnsztajn  ORCID: orcid.org/0000-0003-2950-52833,
  • Aeyal Raz4 &
  • …
  • Hagai Bergman  ORCID: orcid.org/0000-0002-2402-66731,2,5 

Communications Biology , Article number:  (2026) Cite this article

  • 528 Accesses

  • 4 Altmetric

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Neural circuits
  • Neuronal physiology

Abstract

Thalamic neurons discharge tonically during wakefulness and rapid-eye-movement (REM) sleep, but switch to burst firing during non-REM (NREM) sleep. It has been hypothesized that NREM thalamic bursts do not serve as a cortical “wake-up” signal due to their periodic and synchronized nature. Here, we analyze the simultaneously recorded polysomnographic signals, field potentials, and spiking activity of neurons in the ventral anterior and centromedian thalamic nuclei of two female non-human primates during naturally occurring vigilance states. These nuclei receive GABAergic output from the basal ganglia, with discharge rate decreasing during NREM sleep. Despite this reduction in inhibitory input, NREM bursting increases significantly as reported for glutamate-driven thalamic nuclei.  The NREM bursts are neither periodic nor tightly synchronized. However, delta and sleep-spindle EEG activity and thalamic field potentials time-locked to burst onset during NREM sleep markedly differ from those observed during wakefulness and REM sleep. These results suggest that the basal ganglia modulate, rather than drive, their thalamic targets. Additionally, unique state-dependent thalamocortical dynamics, rather than the periodicity or tight synchrony of the thalamic bursts, are sufficient to account for why NREM thalamic bursts do not awaken the cortex.

Similar content being viewed by others

The human thalamus orchestrates neocortical oscillations during NREM sleep

Article Open access 05 September 2022

Alterations in TRN-anterodorsal thalamocortical circuits affect sleep architecture and homeostatic processes in oxidative stress vulnerable Gclm−/− mice

Article Open access 28 July 2022

A temporal sequence of thalamic activity unfolds at transitions in behavioral arousal state

Article Open access 16 September 2022

Data availability

All data supporting the findings of this study are available within the paper as a Supplementary Data. Other data will be available from the corresponding authors upon reasonable request.

Code availability

We provided the code related to the figures of this paper as a Supplementary File. MATLAB code will also be available from the corresponding authors upon reasonable request. Please note that the code used in this study was developed by the researchers for data analysis and visualization. It is intended for research purposes and may not meet professional coding standards.

References

  1. Crunelli, V., Errington, A. C., Hughes, S. W. & Tóth, T. I. The thalamic low-threshold Ca2+ potential: a key determinant of the local and global dynamics of the slow (< 1 Hz) sleep oscillation in thalamocortical networks. Philos. Trans. R. Soc. A Math., Phys. Eng. Sci. 369, 3820–3839 (2011).

    Google Scholar 

  2. Herrera, C. G. & Tarokh, L. A thalamocortical perspective on sleep spindle alterations in neurodevelopmental disorders. Curr. Sleep. Med. Rep. 10, 103–118 (2024).

    Google Scholar 

  3. Schreiner, T., Kaufmann, E., Noachtar, S., Mehrkens, J.-H. & Staudigl, T. The human thalamus orchestrates neocortical oscillations during NREM sleep. Nat. Commun. 13, 5231 (2022).

    Google Scholar 

  4. Gent, T. C., Bandarabadi, M., Herrera, C. G. & Adamantidis, A. R. Thalamic dual control of sleep and wakefulness. Nat. Neurosci. 21, 974–984 (2018).

    Google Scholar 

  5. Jones, E. The core and matrix of thalamic organization. Neuroscience 85, 331–345 (1998).

    Google Scholar 

  6. Usrey, W. M. & Sherman, S. M. The Cerebral Cortex and Thalamus (Oxford Univ. Press, 2024).

  7. Sherman, S. M. & Usrey, W. M. A reconsideration of the core and matrix classification of thalamocortical projections. J. Neurosci. 44,1–4 (2024).

  8. Sherman, S. M. & Guillery, R. W. Exploring the Thalamus and Its Role in Cortical Function (MIT Press, 2006).

  9. Halassa, M. M. The Thalamus (Cambridge Univ. Press, 2022).

  10. Jones, E. G. The Thalamus (Cambridge Univ. Press, 2007).

  11. Shine, J. M. The thalamus integrates the macrosystems of the brain to facilitate complex, adaptive brain network dynamics. Prog. Neurobiol. 199, 101951 (2021).

    Google Scholar 

  12. Weyand, T. G., Boudreaux, M. & Guido, W. Burst and tonic response modes in thalamic neurons during sleep and wakefulness. J. Neurophysiol. 85, 1107–1118 (2001).

    Google Scholar 

  13. McCarley, R. W., Benoit, O. & Barrionuevo, G. Lateral geniculate nucleus unitary discharge in sleep and waking: state- and rate-specific aspects. J. Neurophysiol. 50, 798–818 (1983).

    Google Scholar 

  14. Glenn, L. & Steriade, M. Discharge rate and excitability of cortically projecting intralaminar thalamic neurons during waking and sleep states. J. Neurosci. 2, 1387–1404 (1982).

    Google Scholar 

  15. Sherman, S. M. A wake-up call from the thalamus. Nat. Neurosci. 4, 344–346 (2001).

    Google Scholar 

  16. Ramcharan, E. J., Gnadt, J. W. & Sherman, S. M. Burst and tonic firing in thalamic cells of unanesthetized, behaving monkeys. Vis. Neurosci. 17, 55–62 (2000).

    Google Scholar 

  17. Lisman, J. E. Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci. 20, 38–43 (1997).

    Google Scholar 

  18. Guido, W., Lu, S.-M., Vaughan, J., Godwin, D. W. & Sherman, S. M. Receiver operating characteristic (ROC) analysis of neurons in the cat’s lateral geniculate nucleus during tonic and burst response mode. Vis. Neurosci. 12, 723–741 (1995).

    Google Scholar 

  19. Lüthi, A. & McCormick, D. A. Periodicity of thalamic synchronized oscillations: the role of Ca2+-mediated upregulation of Ih. Neuron 20, 553–563 (1998).

    Google Scholar 

  20. Jahnsen, H. & Llinás, R. Ionic basis for the electro-responsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J. Physiol. 349, 227–247 (1984).

    Google Scholar 

  21. Albin, R. L., Young, A. B. & Penney, J. B. The functional anatomy of basal ganglia disorders. Trends Neurosci. 12, 366–375 (1989).

    Google Scholar 

  22. Bergman, H., Wichmann, T. & DeLong, M. R. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249, 1436–1438 (1990).

    Google Scholar 

  23. Bosch-Bouju, C., Hyland, B. I. & Parr-Brownlie, L. C. Motor thalamus integration of cortical, cerebellar and basal ganglia information: implications for normal and parkinsonian conditions. Front. Comput. Neurosci. 7, 163 (2013).

    Google Scholar 

  24. Mizrahi-Kliger, A. D., Kaplan, A., Israel, Z. & Bergman, H. Desynchronization of slow oscillations in the basal ganglia during natural sleep. Proc. Natl. Acad. Sci. USA 115, E4274–E4283 (2018).

    Google Scholar 

  25. Redinbaugh, M. J. et al. Thalamus modulates consciousness via layer-specific control of cortex. Neuron 106, 66–75. e12 (2020).

    Google Scholar 

  26. Llinás, R. R. & Steriade, M. Bursting of thalamic neurons and states of vigilance. J. Neurophysiol. 95, 3297–3308 (2006).

    Google Scholar 

  27. Bar-Gad, I., Ritov, Y., Vaadia, E. & Bergman, H. Failure in identification of overlapping spikes from multiple neuron activity causes artificial correlations. J. Neurosci. Methods 107, 1–13 (2001).

    Google Scholar 

  28. Perkel, D. H., Gerstein, G. L. & Moore, G. P. Neuronal spike trains and stochastic point processes: II. Simultaneous spike trains. Biophys. J. 7, 419–440 (1967).

    Google Scholar 

  29. Zirh, T., Lenz, F., Reich, S. & Dougherty, P. Patterns of bursting occurring in thalamic cells during Parkinsonian tremor. Neuroscience 83, 107–121 (1998).

    Google Scholar 

  30. Rivlin-Etzion, M., Ritov, Y. A., Heimer, G., Bergman, H. & Bar-Gad, I. Local shuffling of spike trains boosts the accuracy of spike train spectral analysis. J. Neurophysiol. 95, 3245–3256 (2006).

    Google Scholar 

  31. Cox, K. M., Kase, D., Znati, T. & Turner, R. S. Detecting rhythmic spiking through the power spectra of point process model residuals. J. Neural Eng. 21, 046041 (2024).

    Google Scholar 

  32. Heimer, G., Bar-Gad, I., Goldberg, J. A. & Bergman, H. Synchronization of pallidal activity in the MPTP primate model of Parkinsonism is not limited to oscillatory activity. Basal Ganglia VII, 29–34 (2002).

    Google Scholar 

  33. Wong, R. O., Meister, M. & Shatz, C. J. Transient period of correlated bursting activity during development of the mammalian retina. Neuron 11, 923–938 (1993).

    Google Scholar 

  34. Nir, Y. & de Lecea, L. Sleep and vigilance states: embracing spatiotemporal dynamics. Neuron 111, 1998–2011 (2023).

    Google Scholar 

  35. dos Santos Lima, G. Z. et al. Hippocampal and cortical communication around micro-arousals in slow-wave sleep. Sci. Rep. 9, 5876 (2019).

    Google Scholar 

  36. Logothetis, N. K., Kayser, C. & Oeltermann, A. In vivo measurement of cortical impedance spectrum in monkeys: implications for signal propagation. Neuron 55, 809–823 (2007).

    Google Scholar 

  37. Marmor, O. et al. Local vs. volume conductance activity of field potentials in the human subthalamic nucleus. J. Neurophysiol. 117, 2140–2151 (2017).

    Google Scholar 

  38. Churchland, M. M. & Shenoy, K. V. Preparatory activity and the expansive null-space. Nat. Rev. Neurosci. 25, 213–236 (2024).

    Google Scholar 

  39. Vishwanath, A., Bartlett, M. J., Falk, T. & Cowen, S. L. Decoupling of motor cortex to movement in Parkinson’s dyskinesia rescued by sub-anaesthetic ketamine. Brain 148, 2135–2150 (2025).

    Google Scholar 

  40. Ben-Ari, Y. The GABA excitatory/inhibitory developmental sequence: a personal journey. Neuroscience 279, 187–219 (2014).

    Google Scholar 

  41. Mink, J. W. The basal ganglia: focused selection and inhibition of competing motor programs. Prog. Neurobiol. 50, 381–425 (1996).

    Google Scholar 

  42. Schwab, B. C. et al. Neural activity during a simple reaching task in macaques is counter to gating and rebound in basal ganglia–thalamic communication. PLoS Biol. 18, e3000829 (2020).

    Google Scholar 

  43. Goldberg, J. H., Farries, M. A. & Fee, M. S. Basal ganglia output to the thalamus: still a paradox. Trends Neurosci. 36, 695–705 (2013).

    Google Scholar 

  44. Adler, A. et al. Neurons in both pallidal segments change their firing properties similarly prior to closure of the eyes. J. Neurophysiol. 103, 346–359 (2010).

    Google Scholar 

  45. Timofeev, I., Grenier, F. & Steriade, M. Impact of intrinsic properties and synaptic factors on the activity of neocortical networks in vivo. J. Physiol. Paris 94, 343–355 (2000).

    Google Scholar 

  46. Crunelli, V. et al. Dual function of thalamic low-vigilance state oscillations: rhythm-regulation and plasticity. Nat. Rev. Neurosci. 19, 107–118 (2018).

    Google Scholar 

  47. Steriade, M., Contreras, D. & Amzica, F. Synchronized sleep oscillations and their paroxysmal developments. Trends Neurosci. 17, 201–207 (1994).

    Google Scholar 

  48. Contreras, D., Destexhe, A. & Steriade, M. Intracellular and computational characterization of the intracortical inhibitory control of synchronized thalamic inputs in vivo. J. Neurophysiol. 78, 335–350 (1997).

    Google Scholar 

  49. Steriade, M., McCormick, D. A. & Sejnowski, T. J. Thalamocortical oscillations in the sleeping and aroused brain. Science 262, 679–685 (1993).

    Google Scholar 

  50. Nir, Y. & Tononi, G. Dreaming and the brain: from phenomenology to neurophysiology. Trends Cogn. Sci. 14, 88–100 (2010).

    Google Scholar 

  51. Steriade, M. & McCarley, R. W. Neuronal activities in brainstem and basal forebrain structures controlling waking and sleep states. In Brain Control of Wakefulness Sleep 381–416 (Springer, Boston, MA, 2005).

  52. Mizrahi-Kliger, A. D., Kaplan, A., Israel, Z., Deffains, M. & Bergman, H. Basal ganglia beta oscillations during sleep underlie Parkinsonian insomnia. Proc. Natl. Acad. Sci. USA 117, 17359–17368 (2020).

    Google Scholar 

  53. Hsieh, K.-C., Robinson, E. L. & Fuller, C. A. Sleep architecture in unrestrained rhesus monkeys (Macaca mulatta) synchronized to 24-hour light-dark cycles. Sleep 31, 1239–1250 (2008).

    Google Scholar 

  54. Reite, M., Rhodes, J., Kavan, E. & Adey, W. Normal sleep patterns in macaque monkey. Arch. Neurol. 12, 133–144 (1965).

    Google Scholar 

  55. Hagenauer, M. H. & Lee, T. M. Adolescent sleep patterns in humans and laboratory animals. Hormones Behav. 64, 270–279 (2013).

    Google Scholar 

  56. Hirshkowitz, M. Normal human sleep: an overview. Med. Clin. 88, 551–565 (2004).

    Google Scholar 

  57. Scala, F. et al. Phenotypic variation of transcriptomic cell types in mouse motor cortex. Nature 598, 144–150 (2021).

    Google Scholar 

  58. Council, N. R. et al. Guide for the Care and Use of Laboratory Animals 8th edn (National Academies Press, 2011).

  59. Robinson, D. A. A method of measuring eye movemnent using a scieral search coil in a magnetic field. IEEE Trans. Biomed. Electron. 10, 137–145 (1963).

    Google Scholar 

  60. Glowinsky, S., Israel, Z., Heymann, S. & Bergman, H. Divide and conquer: automatic detection of the thalamus to empower DBS physiological navigation to the subthalamic region. IEEE Trans. Neural Syst. Rehabil. Eng. 33, 2672–2683 (2025).

  61. Guang, J. et al. Toward asleep DBS: cortico-basal ganglia spectral and coherence activity during interleaved propofol/ketamine sedation mimics NREM/REM sleep activity. npj Parkinsons. Dis. 7, 67 (2021).

    Google Scholar 

  62. Goshtasby, A. Image registration by local approximation methods. Image Vis. Comput. 6, 255–261 (1988).

    Google Scholar 

  63. Joshua, M., Elias, S., Levine, O. & Bergman, H. Quantifying the isolation quality of extracellularly recorded action potentials. J. Neurosci. Methods 163, 267–282 (2007).

    Google Scholar 

  64. Cotterill, E. & Eglen, S. Burst detection methods. In In Vitro Neuronal Networks. Advances in Neurobiology (eds Chiappalone, M. et al.) Vol 22, 185–206 (Springer, Cham, 2019).

  65. Legendy, C. & Salcman, M. Bursts and recurrences of bursts in the spike trains of spontaneously active striate cortex neurons. J. Neurophysiol. 53, 926–939 (1985).

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank Uri Werner-Reiss, PhD, for his valuable support with the surgical procedures and all aspects of monkey care, Tamar Ravins Yaish, DMD, and the HUJI-ELSC animal facility team for their assistance. We thank Ad Aertsen for the fruitful discussion of correlation analysis and the association index, and Andy Horn, Jackie Schiller, Pnina Rapel, Aric Agmon, and Yuval Nir for their discussions and comments on early versions of the manuscript. We acknowledge the use of large language model (LLM) tools for linguistic editing to improve the clarity and grammar of this manuscript; no scientific content was generated by these tools. This study is supported by grants from the ISF Breakthrough Research program (Grant No.: 1738/22) and the Collaborative Research Center TRR295, Germany (Project number 424778381) to HB.

Author information

Author notes
  1. These authors contributed equally: Xiaowei Liu, Jing Guang.

Authors and Affiliations

  1. The Edmond and Lily Safra Center for Brain Science, The Hebrew University, Jerusalem, Israel

    Xiaowei Liu, Jing Guang & Hagai Bergman

  2. Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel

    Zvi Israel & Hagai Bergman

  3. Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel

    Denise Wajnsztajn

  4. Department of Anaesthesiology, Rambam Health Care Campus, Haifa, Israel

    Aeyal Raz

  5. Department of Medical Neurobiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

    Hagai Bergman

Authors
  1. Xiaowei Liu
    View author publications

    Search author on:PubMed Google Scholar

  2. Jing Guang
    View author publications

    Search author on:PubMed Google Scholar

  3. Zvi Israel
    View author publications

    Search author on:PubMed Google Scholar

  4. Denise Wajnsztajn
    View author publications

    Search author on:PubMed Google Scholar

  5. Aeyal Raz
    View author publications

    Search author on:PubMed Google Scholar

  6. Hagai Bergman
    View author publications

    Search author on:PubMed Google Scholar

Contributions

J.G. and H.B. conceived the research and designed the experiments. Z.I., D.W., and A.R. performed the surgical procedure. X.L. and J.G. supported the surgical procedure. They also performed the experiments, including electrophysiological and behavioral recordings, analyzed the data, and conducted the statistical analysis. X.L., J.G., and H.B. prepared the figures and wrote the manuscript. H.B. supervised the work. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiaowei Liu or Jing Guang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Communications Biology thanks Takeshi Kanda, Joaquín González, and the other anonymous reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Benjamin Bessieres.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information

Description of Additional Supplementary Files

Supplementary data

Reporting Summary

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Guang, J., Israel, Z. et al. Entrained cortical delta–spindle activity, not periodic synchrony, prevents arousal by NREM thalamic bursts. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09565-3

Download citation

  • Received: 24 September 2025

  • Accepted: 09 January 2026

  • Published: 23 January 2026

  • DOI: https://doi.org/10.1038/s42003-026-09565-3

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open Access Fees and Funding
  • Journal Metrics
  • Editors
  • Editorial Board
  • Calls for Papers
  • Referees
  • Contact
  • Editorial policies
  • Aims & Scope

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Communications Biology (Commun Biol)

ISSN 2399-3642 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing