IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-62317-5.html
   My bibliography  Save this article

Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control

Author

Listed:
  • Yuxiang Andy Liu

    (500 W 120th St)

  • Yuhan Nong

    (500 W 120th St)

  • Jiesi Feng

    (Peking University
    PKU-IDG/McGovern Institute for Brain Research)

  • Guochuan Li

    (Peking University
    PKU-IDG/McGovern Institute for Brain Research)

  • Paul Sajda

    (500 W 120th St)

  • Yulong Li

    (Peking University
    PKU-IDG/McGovern Institute for Brain Research)

  • Qi Wang

    (500 W 120th St)

Abstract

This study investigates how norepinephrine (NE) and acetylcholine (ACh) in the prefrontal cortex (PFC) modulate inhibitory control, a critical executive function. Using fluorescent sensors, we tracked prefrontal NE/ACh dynamics in mice during inhibitory control tasks and found strong NE-ACh coherence at 0.4–0.8 Hz. Inhibiting locus coeruleus (LC) neurons projecting to the basal forebrain (BF) induced greater impairments in inhibitory control than targeting those projecting to the PFC, despite partial overlap. This inhibition disrupted NE-ACh phase synchrony between successful and failed trials, indicating its importance. Conversely, silencing cholinergic neurons projecting to the LC did not affect task performance or phase synchrony. Neuropixels recordings revealed that disrupting LC-BF projections impaired PFC neuronal encoding and altered population firing patterns linked to inhibitory control. These findings suggest that the LC and cholinergic systems jointly modulate inhibitory control by influencing NE-ACh synchrony and its effect on PFC activity, underscoring their role in cognitive control.

Suggested Citation

  • Yuxiang Andy Liu & Yuhan Nong & Jiesi Feng & Guochuan Li & Paul Sajda & Yulong Li & Qi Wang, 2025. "Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62317-5
    DOI: 10.1038/s41467-025-62317-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-62317-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-62317-5?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. Anne C. Krok & Marta Maltese & Pratik Mistry & Xiaolei Miao & Yulong Li & Nicolas X. Tritsch, 2023. "Intrinsic dopamine and acetylcholine dynamics in the striatum of mice," Nature, Nature, vol. 621(7979), pages 543-549, September.
    2. Lindsay A. Schwarz & Kazunari Miyamichi & Xiaojing J. Gao & Kevin T. Beier & Brandon Weissbourd & Katherine E. DeLoach & Jing Ren & Sandy Ibanes & Robert C. Malenka & Eric J. Kremer & Liqun Luo, 2015. "Viral-genetic tracing of the input–output organization of a central noradrenaline circuit," Nature, Nature, vol. 524(7563), pages 88-92, August.
    3. Kathy Y. Liu & Rogier A. Kievit & Kamen A. Tsvetanov & Matthew J. Betts & Emrah Düzel & James B. Rowe & Robert Howard & Dorothea Hämmerer, 2020. "Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    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. Chi Geng & Ruochen Li & Shan Li & Penglai Liu & Yuxin Peng & Changyu Liu & Zhen Wang & Hongxing Zhang & Anan Li, 2025. "Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    2. Mite Mijalkov & Ludvig Storm & Blanca Zufiria-Gerbolés & Dániel Veréb & Zhilei Xu & Anna Canal-Garcia & Jiawei Sun & Yu-Wei Chang & Hang Zhao & Emiliano Gómez-Ruiz & Massimiliano Passaretti & Sara Gar, 2025. "Computational memory capacity predicts aging and cognitive decline," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    3. Michellee M. Garcia & Amber M. Kline & Koun Onodera & Hiroaki Tsukano & Pranathi R. Dandu & Hailey C. Acosta & Michael R. Kasten & Paul B. Manis & Hiroyuki K. Kato, 2025. "Noncanonical short-latency auditory pathway directly activates deep cortical layers," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    4. Safa Bouabid & Liangzhu Zhang & Mai-Anh T. Vu & Kylie Tang & Benjamin M. Graham & Christian A. Noggle & Mark W. Howe, 2025. "Distinct spatially organized striatum-wide acetylcholine dynamics for the learning and extinction of Pavlovian associations," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    5. Xiaolong Gao & Huan Wei & Wenjie Ma & Wenjie Wu & Wenliang Ji & Junjie Mao & Ping Yu & Lanqun Mao, 2024. "Inflammation-free electrochemical in vivo sensing of dopamine with atomic-level engineered antioxidative single-atom catalyst," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Esra Senol & Menghan Wang & Yongjuan Xin & Zhuolei Jiao & Hasan Mohammad & Xin Yi Yeo & Tengxiao Si & David M. Young & Hua Huang & Yingxue Wang & Qin Li & Sang Yong Jung & Xiaohong Xu & Pei Zhang & Yu, 2025. "Brain-wide input-output analysis of tuberal nucleus somatostatin neurons reveals hierarchical circuits for orchestrating feeding behavior," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    7. Feng Xiong & Hong Yang & Yi-Ge Song & Hai-Bin Qin & Qing-Yang Zhang & Xian Huang & Wei Jing & Manfei Deng & Yang Liu & Zhixiang Liu & Yin Shen & Yunyun Han & Youming Lu & Xiangmin Xu & Todd C. Holmes , 2022. "An HSV-1-H129 amplicon tracer system for rapid and efficient monosynaptic anterograde neural circuit tracing," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Lior Matityahu & Naomi Gilin & Gideon A. Sarpong & Yara Atamna & Lior Tiroshi & Nicolas X. Tritsch & Jeffery R. Wickens & Joshua A. Goldberg, 2023. "Acetylcholine waves and dopamine release in the striatum," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    9. Prokopis C. Prokopiou & Nina Engels-Domínguez & Kathryn V. Papp & Matthew R. Scott & Aaron P. Schultz & Christoph Schneider & Michelle E. Farrell & Rachel F. Buckley & Yakeel T. Quiroz & Georges El Fa, 2022. "Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Min Jung Kim & Daniel J. Gibson & Dan Hu & Tomoko Yoshida & Emily Hueske & Ayano Matsushima & Ara Mahar & Cynthia J. Schofield & Patlapa Sompolpong & Kathy T. Tran & Lin Tian & Ann M. Graybiel, 2024. "Dopamine release plateau and outcome signals in dorsal striatum contrast with classic reinforcement learning formulations," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    11. Xin-Yue Wang & Wen-Bin Jia & Xiang Xu & Rui Chen & Liang-Biao Wang & Xiao-Jing Su & Peng-Fei Xu & Xiao-Qing Liu & Jie Wen & Xiao-Yuan Song & Yuan-Yuan Liu & Zhi Zhang & Xin-Feng Liu & Yan Zhang, 2023. "A glutamatergic DRN–VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice," Nature Communications, Nature, vol. 14(1), pages 1-15, 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_s41467-025-62317-5. 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.