IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43142-0.html
   My bibliography  Save this article

Functional alterations of the prefrontal circuit underlying cognitive aging in mice

Author

Listed:
  • Huee Ru Chong

    (Nanyang Technological University)

  • Yadollah Ranjbar-Slamloo

    (Nanyang Technological University)

  • Malcolm Zheng Hao Ho

    (Nanyang Technological University
    Nanyang Technological University)

  • Xuan Ouyang

    (Nanyang Technological University)

  • Tsukasa Kamigaki

    (Nanyang Technological University)

Abstract

Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in the mouse medial prefrontal cortex (mPFC) are altered as early as middle age. Population activity in the young adult mPFC exhibits dissociable yet overlapping patterns between tactile and auditory modalities, enabling crossmodal memory coding concurrent with modality-dependent coding. In middle age, however, crossmodal coding remarkably diminishes while modality-dependent coding persists, and both types of coding decay in advanced age. Resting-state functional connectivity, especially among memory-coding neurons, decreases already in middle age, suggesting deteriorated recurrent circuits for memory maintenance. Optogenetic inactivation reveals that the middle-aged mPFC exhibits heightened vulnerability to perturbations. These findings elucidate functional alterations of the prefrontal circuit that unfold in middle age and deteriorate further as a hallmark of cognitive aging.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43142-0
    DOI: 10.1038/s41467-023-43142-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43142-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43142-0?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. Ivan Voitov & Thomas D. Mrsic-Flogel, 2022. "Cortical feedback loops bind distributed representations of working memory," Nature, Nature, vol. 608(7922), pages 381-389, August.
    2. Joaquín M. Fuster & Mark Bodner & James K. Kroger, 2000. "Cross-modal and cross-temporal association in neurons of frontal cortex," Nature, Nature, vol. 405(6784), pages 347-351, May.
    3. Matthew F. Panichello & Timothy J. Buschman, 2021. "Shared mechanisms underlie the control of working memory and attention," Nature, Nature, vol. 592(7855), pages 601-605, April.
    4. Min Wang & Nao J. Gamo & Yang Yang & Lu E. Jin & Xiao-Jing Wang & Mark Laubach & James A. Mazer & Daeyeol Lee & Amy F. T. Arnsten, 2011. "Neuronal basis of age-related working memory decline," Nature, Nature, vol. 476(7359), pages 210-213, August.
    5. Jung Won Bae & Huijeong Jeong & Young Ju Yoon & Chan Mee Bae & Hyeonsu Lee & Se-Bum Paik & Min Whan Jung, 2021. "Parallel processing of working memory and temporal information by distinct types of cortical projection neurons," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    6. Alon Rubin & Liron Sheintuch & Noa Brande-Eilat & Or Pinchasof & Yoav Rechavi & Nitzan Geva & Yaniv Ziv, 2019. "Revealing neural correlates of behavior without behavioral measurements," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    7. Nuo Li & Kayvon Daie & Karel Svoboda & Shaul Druckmann, 2016. "Correction: Corrigendum: Robust neuronal dynamics in premotor cortex during motor planning," Nature, Nature, vol. 537(7618), pages 122-122, September.
    8. Zhenyu Gao & Courtney Davis & Alyse M. Thomas & Michael N. Economo & Amada M. Abrego & Karel Svoboda & Chris I. Zeeuw & Nuo Li, 2018. "A cortico-cerebellar loop for motor planning," Nature, Nature, vol. 563(7729), pages 113-116, November.
    9. 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.
    10. J. L. Vincent & G. H. Patel & M. D. Fox & A. Z. Snyder & J. T. Baker & D. C. Van Essen & J. M. Zempel & L. H. Snyder & M. Corbetta & M. E. Raichle, 2007. "Intrinsic functional architecture in the anaesthetized monkey brain," Nature, Nature, vol. 447(7140), pages 83-86, May.
    11. Mathias Mahn & Lihi Gibor & Pritish Patil & Katayun Cohen-Kashi Malina & Shir Oring & Yoav Printz & Rivka Levy & Ilan Lampl & Ofer Yizhar, 2018. "High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    12. Chunyu A. Duan & Yuxin Pan & Guofen Ma & Taotao Zhou & Siyu Zhang & Ning-long Xu, 2021. "A cortico-collicular pathway for motor planning in a memory-dependent perceptual decision task," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    13. Nuo Li & Kayvon Daie & Karel Svoboda & Shaul Druckmann, 2016. "Robust neuronal dynamics in premotor cortex during motor planning," Nature, Nature, vol. 532(7600), pages 459-464, April.
    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. Xin Wei Chia & Jian Kwang Tan & Lee Fang Ang & Tsukasa Kamigaki & Hiroshi Makino, 2023. "Emergence of cortical network motifs for short-term memory during learning," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Alyse Thomas & Weiguo Yang & Catherine Wang & Sri Laasya Tipparaju & Guang Chen & Brennan Sullivan & Kylie Swiekatowski & Mahima Tatam & Charles Gerfen & Nuo Li, 2023. "Superior colliculus bidirectionally modulates choice activity in frontal cortex," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. 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.
    4. J. Tyler Boyd-Meredith & Alex T. Piet & Emily Jane Dennis & Ahmed El Hady & Carlos D. Brody, 2022. "Stable choice coding in rat frontal orienting fields across model-predicted changes of mind," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. João D. Semedo & Anna I. Jasper & Amin Zandvakili & Aravind Krishna & Amir Aschner & Christian K. Machens & Adam Kohn & Byron M. Yu, 2022. "Feedforward and feedback interactions between visual cortical areas use different population activity patterns," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Tanner C Dixon & Christina M Merrick & Joni D Wallis & Richard B Ivry & Jose M Carmena, 2021. "Hybrid dedicated and distributed coding in PMd/M1 provides separation and interaction of bilateral arm signals," PLOS Computational Biology, Public Library of Science, vol. 17(11), pages 1-35, November.
    7. Christopher F. Angeloni & Wiktor Młynarski & Eugenio Piasini & Aaron M. Williams & Katherine C. Wood & Linda Garami & Ann M. Hermundstad & Maria N. Geffen, 2023. "Dynamics of cortical contrast adaptation predict perception of signals in noise," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Maria Wilhelm & Yaroslav Sych & Aleksejs Fomins & José Luis Alatorre Warren & Christopher Lewis & Laia Serratosa Capdevila & Roman Boehringer & Elizabeth A. Amadei & Benjamin Grewe & Eoin C. O’Connor , 2023. "Striatum-projecting prefrontal cortex neurons support working memory maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Protachevicz, Paulo Ricardo & Borges, Fernando da Silva & Batista, Antonio Marcos & Baptista, Murilo da Silva & Caldas, Iberê Luiz & Macau, Elbert Einstein Nehrer & Lameu, Ewandson Luiz, 2023. "Plastic neural network with transmission delays promotes equivalence between function and structure," Chaos, Solitons & Fractals, Elsevier, vol. 171(C).
    10. Laura Biagi & Sofia Allegra Crespi & Michela Tosetti & Maria Concetta Morrone, 2015. "BOLD Response Selective to Flow-Motion in Very Young Infants," PLOS Biology, Public Library of Science, vol. 13(9), pages 1-22, September.
    11. Alessandra Griffa & Mathieu Mach & Julien Dedelley & Daniel Gutierrez-Barragan & Alessandro Gozzi & Gilles Allali & Joanes Grandjean & Dimitri Ville & Enrico Amico, 2023. "Evidence for increased parallel information transmission in human brain networks compared to macaques and male mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. 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.
    13. 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.
    14. Mehrabbeik, Mahtab & Shams-Ahmar, Mohammad & Levine, Alexandra T. & Jafari, Sajad & Merrikhi, Yaser, 2022. "Distinctive nonlinear dimensionality of neural spiking activity in extrastriate cortex during spatial working memory; a Higuchi fractal analysis," Chaos, Solitons & Fractals, Elsevier, vol. 158(C).
    15. Anandamohan Ghosh & Y Rho & A R McIntosh & R Kötter & V K Jirsa, 2008. "Noise during Rest Enables the Exploration of the Brain's Dynamic Repertoire," PLOS Computational Biology, Public Library of Science, vol. 4(10), pages 1-12, October.
    16. Baiwei Liu & Anna C. Nobre & Freek van Ede, 2022. "Functional but not obligatory link between microsaccades and neural modulation by covert spatial attention," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    17. Chaogan Yan & Dongqiang Liu & Yong He & Qihong Zou & Chaozhe Zhu & Xinian Zuo & Xiangyu Long & Yufeng Zang, 2009. "Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load," PLOS ONE, Public Library of Science, vol. 4(5), pages 1-11, May.
    18. Mikael Lundqvist & Scott L. Brincat & Jonas Rose & Melissa R. Warden & Timothy J. Buschman & Earl K. Miller & Pawel Herman, 2023. "Working memory control dynamics follow principles of spatial computing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    19. Ken-ichi Okada & Ryuji Takeya & Masaki Tanaka, 2022. "Neural signals regulating motor synchronization in the primate deep cerebellar nuclei," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Joao Barbosa & Rémi Proville & Chris C. Rodgers & Michael R. DeWeese & Srdjan Ostojic & Yves Boubenec, 2023. "Early selection of task-relevant features through population gating," Nature Communications, Nature, vol. 14(1), pages 1-13, 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:14:y:2023:i:1:d:10.1038_s41467-023-43142-0. 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.