IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-62498-z.html
   My bibliography  Save this article

Time cell sequences during delay intervals are not dependent on brain state and do not support hippocampus-dependent working memory

Author

Listed:
  • Li Yuan

    (University of California San Diego)

  • Jose F. Figueroa

    (University of California San Diego)

  • Ameen Khan

    (University of California San Diego)

  • Gautam Narayan

    (University of California San Diego)

  • Jill K. Leutgeb

    (University of California San Diego
    Institute for Advanced Study
    University of California San Diego)

  • Stefan Leutgeb

    (University of California San Diego
    Institute for Advanced Study
    University of California San Diego)

Abstract

Working memory (WM) is essential for performing cognitive tasks, and sequentially active hippocampal cells over many seconds (‘time cells’) have been observed during WM retention. Time cells predominantly occur when neural activity oscillates at theta frequency. To examine whether time cells during WM maintenance depend on ongoing theta oscillations, we controlled the persistence of theta during 10 s and 30 s delay intervals by either having rats run or rest, which resulted in conditions with and without persistent theta oscillations. In either condition, reliable time cells were limited to only the first few seconds of the delay interval while a second population of constitutively active cells emerged during the remainder of the delay period, neither of which were memory-related. Our results show that hippocampal sequential activity patterns are short-lasting and uninformative for WM, and that WM retention over more than ~5 s needs to include mechanisms other than hippocampal time cells.

Suggested Citation

  • Li Yuan & Jose F. Figueroa & Ameen Khan & Gautam Narayan & Jill K. Leutgeb & Stefan Leutgeb, 2025. "Time cell sequences during delay intervals are not dependent on brain state and do not support hippocampus-dependent working memory," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62498-z
    DOI: 10.1038/s41467-025-62498-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-62498-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-62498-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Brad E. Pfeiffer & David J. Foster, 2013. "Hippocampal place-cell sequences depict future paths to remembered goals," Nature, Nature, vol. 497(7447), pages 74-79, May.
    2. Hiroshi T. Ito & Sheng-Jia Zhang & Menno P. Witter & Edvard I. Moser & May-Britt Moser, 2015. "A prefrontal–thalamo–hippocampal circuit for goal-directed spatial navigation," Nature, Nature, vol. 522(7554), pages 50-55, June.
    3. Timothy Spellman & Mattia Rigotti & Susanne E. Ahmari & Stefano Fusi & Joseph A. Gogos & Joshua A. Gordon, 2015. "Hippocampal–prefrontal input supports spatial encoding in working memory," Nature, Nature, vol. 522(7556), pages 309-314, June.
    4. James J. Jun & Nicholas A. Steinmetz & Joshua H. Siegle & Daniel J. Denman & Marius Bauza & Brian Barbarits & Albert K. Lee & Costas A. Anastassiou & Alexandru Andrei & Çağatay Aydın & Mladen Barbic &, 2017. "Fully integrated silicon probes for high-density recording of neural activity," Nature, Nature, vol. 551(7679), pages 232-236, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hannah Muysers & Hung-Ling Chen & Johannes Hahn & Shani Folschweiller & Torfi Sigurdsson & Jonas-Frederic Sauer & Marlene Bartos, 2024. "A persistent prefrontal reference frame across time and task rules," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Toon Van de Maele & Bart Dhoedt & Tim Verbelen & Giovanni Pezzulo, 2024. "A hierarchical active inference model of spatial alternation tasks and the hippocampal-prefrontal circuit," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Jordan Crivelli-Decker & Alex Clarke & Seongmin A. Park & Derek J. Huffman & Erie D. Boorman & Charan Ranganath, 2023. "Goal-oriented representations in the human hippocampus during planning and navigation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Spencer Ward & Conor Riley & Erin M. Carey & Jenny Nguyen & Sadik Esener & Axel Nimmerjahn & Donald J. Sirbuly, 2022. "Electro-optical mechanically flexible coaxial microprobes for minimally invasive interfacing with intrinsic neural circuits," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Huee Ru Chong & Yadollah Ranjbar-Slamloo & Malcolm Zheng Hao Ho & Xuan Ouyang & Tsukasa Kamigaki, 2023. "Functional alterations of the prefrontal circuit underlying cognitive aging in mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. J Matthew Mahoney & Ali S Titiz & Amanda E Hernan & Rod C Scott, 2016. "Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay," PLOS ONE, Public Library of Science, vol. 11(2), pages 1-25, February.
    7. Marta Huelin Gorriz & Masahiro Takigawa & Daniel Bendor, 2023. "The role of experience in prioritizing hippocampal replay," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Li Zheng & Zhiyao Gao & Andrew S. McAvan & Eve A. Isham & Arne D. Ekstrom, 2021. "Partially overlapping spatial environments trigger reinstatement in hippocampus and schema representations in prefrontal cortex," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    9. Nicolas Cazin & Martin Llofriu Alonso & Pablo Scleidorovich Chiodi & Tatiana Pelc & Bruce Harland & Alfredo Weitzenfeld & Jean-Marc Fellous & Peter Ford Dominey, 2019. "Reservoir computing model of prefrontal cortex creates novel combinations of previous navigation sequences from hippocampal place-cell replay with spatial reward propagation," PLOS Computational Biology, Public Library of Science, vol. 15(7), pages 1-32, July.
    10. Liang Zou & Huihui Tian & Shouliang Guan & Jianfei Ding & Lei Gao & Jinfen Wang & Ying Fang, 2021. "Self-assembled multifunctional neural probes for precise integration of optogenetics and electrophysiology," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    11. repec:plo:pcbi00:1006854 is not listed on IDEAS
    12. Shailaja Akella & Peter Ledochowitsch & Joshua H. Siegle & Hannah Belski & Daniel D. Denman & Michael A. Buice & Severine Durand & Christof Koch & Shawn R. Olsen & Xiaoxuan Jia, 2025. "Deciphering neuronal variability across states reveals dynamic sensory encoding," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    13. Yoav Printz & Pritish Patil & Mathias Mahn & Asaf Benjamin & Anna Litvin & Rivka Levy & Max Bringmann & Ofer Yizhar, 2023. "Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Yann Vanrobaeys & Utsav Mukherjee & Lucy Langmack & Stacy E. Beyer & Ethan Bahl & Li-Chun Lin & Jacob J. Michaelson & Ted Abel & Snehajyoti Chatterjee, 2023. "Mapping the spatial transcriptomic signature of the hippocampus during memory consolidation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. Hadar Yaakov & Alina S. Heukamp & Serena Riccitelli & Michal Rivlin-Etzion, 2025. "Differential topographic organization and retinal inheritance of direction and orientation selectivity in the visual thalamus," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    16. Maanasa Jayachandran & Tatiana D. Viena & Andy Garcia & Abdiel Vasallo Veliz & Sofia Leyva & Valentina Roldan & Robert P. Vertes & Timothy A. Allen, 2023. "Nucleus reuniens transiently synchronizes memory networks at beta frequencies," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Elisabeta Balla & Gerion Nabbefeld & Christopher Wiesbrock & Jenice Linde & Severin Graff & Simon Musall & Björn M. Kampa, 2025. "Broadband visual stimuli improve neuronal representation and sensory perception," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    18. repec:plo:pcbi00:1006370 is not listed on IDEAS
    19. Keundong Lee & Angelique C. Paulk & Yun Goo Ro & Daniel R. Cleary & Karen J. Tonsfeldt & Yoav Kfir & John S. Pezaris & Youngbin Tchoe & Jihwan Lee & Andrew M. Bourhis & Ritwik Vatsyayan & Joel R. Mart, 2024. "Flexible, scalable, high channel count stereo-electrode for recording in the human brain," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    20. Andrea Santoro & Federico Battiston & Maxime Lucas & Giovanni Petri & Enrico Amico, 2024. "Higher-order connectomics of human brain function reveals local topological signatures of task decoding, individual identification, and behavior," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    21. Gustavo Della-Flora Nunes & Lindsay A. Osso & Johana A. Haynes & Lauren Conant & Michael A. Thornton & Michael E. Stockton & Katherine A. Brassell & Amanda Morris & Yessenia I. Mancha Corchado & John , 2025. "Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    22. Edward A. B. Horrocks & Fabio R. Rodrigues & Aman B. Saleem, 2024. "Flexible neural population dynamics govern the speed and stability of sensory encoding in mouse visual cortex," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62498-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.