IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41026-x.html
   My bibliography  Save this article

Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model

Author

Listed:
  • Bastijn J. G. Boom

    (Royal Netherlands Academy of Arts and Sciences
    University of Amsterdam)

  • Alfredo Elhazaz-Fernandez

    (Royal Netherlands Academy of Arts and Sciences)

  • Peter A. Rasmussen

    (Royal Netherlands Academy of Arts and Sciences)

  • Enny H. Beest

    (Royal Netherlands Academy of Arts and Sciences)

  • Aishwarya Parthasarathy

    (Royal Netherlands Academy of Arts and Sciences
    University of Amsterdam)

  • Damiaan Denys

    (University of Amsterdam)

  • Ingo Willuhn

    (Royal Netherlands Academy of Arts and Sciences
    University of Amsterdam)

Abstract

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.

Suggested Citation

  • Bastijn J. G. Boom & Alfredo Elhazaz-Fernandez & Peter A. Rasmussen & Enny H. Beest & Aishwarya Parthasarathy & Damiaan Denys & Ingo Willuhn, 2023. "Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41026-x
    DOI: 10.1038/s41467-023-41026-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41026-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41026-x?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. Pino Alonso & Daniel Cuadras & Loes Gabriëls & Damiaan Denys & Wayne Goodman & Ben D Greenberg & Fiacro Jimenez-Ponce & Jens Kuhn & Doris Lenartz & Luc Mallet & Bart Nuttin & Eva Real & Cinto Segalas , 2015. "Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-16, July.
    2. Eric Lowet & Krishnakanth Kondabolu & Samuel Zhou & Rebecca A. Mount & Yangyang Wang & Cara R. Ravasio & Xue Han, 2022. "Deep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus," Nature Communications, Nature, vol. 13(1), pages 1-15, 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. Sudiksha Sridhar & Eric Lowet & Howard J. Gritton & Jennifer Freire & Chengqian Zhou & Florence Liang & Xue Han, 2024. "Beta-frequency sensory stimulation enhances gait rhythmicity through strengthened coupling between striatal networks and stepping movement," Nature Communications, Nature, vol. 15(1), pages 1-17, 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_s41467-023-41026-x. 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.