IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v557y2018i7704d10.1038_s41586-018-0090-6.html
   My bibliography  Save this article

Diametric neural ensemble dynamics in parkinsonian and dyskinetic states

Author

Listed:
  • Jones G. Parker

    (Stanford University
    Pfizer Inc.)

  • Jesse D. Marshall

    (Stanford University
    Stanford University
    Harvard University)

  • Biafra Ahanonu

    (Stanford University
    Stanford University)

  • Yu-Wei Wu

    (Stanford University School of Medicine)

  • Tony Hyun Kim

    (Stanford University)

  • Benjamin F. Grewe

    (Stanford University
    University of Zürich and ETH Zürich)

  • Yanping Zhang

    (Stanford University
    Stanford University)

  • Jin Zhong Li

    (Stanford University
    Cegeim Bio-Engineering (Changchun) Co. Ltd.)

  • Jun B. Ding

    (Stanford University School of Medicine)

  • Michael D. Ehlers

    (Pfizer Inc.
    Biogen)

  • Mark J. Schnitzer

    (Stanford University
    Stanford University)

Abstract

Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson’s disease with the dopamine precursor l-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during l-DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, l-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in l-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.

Suggested Citation

  • Jones G. Parker & Jesse D. Marshall & Biafra Ahanonu & Yu-Wei Wu & Tony Hyun Kim & Benjamin F. Grewe & Yanping Zhang & Jin Zhong Li & Jun B. Ding & Michael D. Ehlers & Mark J. Schnitzer, 2018. "Diametric neural ensemble dynamics in parkinsonian and dyskinetic states," Nature, Nature, vol. 557(7704), pages 177-182, May.
  • Handle: RePEc:nat:nature:v:557:y:2018:i:7704:d:10.1038_s41586-018-0090-6
    DOI: 10.1038/s41586-018-0090-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0090-6
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-018-0090-6?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Bérénice Coutant & Jimena Laura Frontera & Elodie Perrin & Adèle Combes & Thibault Tarpin & Fabien Menardy & Caroline Mailhes-Hamon & Sylvie Perez & Bertrand Degos & Laurent Venance & Clément Léna & D, 2022. "Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Christophe Varin & Amandine Cornil & Delphine Houtteman & Patricia Bonnavion & Alban Kerchove d’Exaerde, 2023. "The respective activation and silencing of striatal direct and indirect pathway neurons support behavior encoding," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Sean C. Piantadosi & Elizabeth E. Manning & Brittany L. Chamberlain & James Hyde & Zoe LaPalombara & Nicholas M. Bannon & Jamie L. Pierson & Vijay M. K Namboodiri & Susanne E. Ahmari, 2024. "Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Allen P. F. Chen & Lu Chen & Kaiyo W. Shi & Eileen Cheng & Shaoyu Ge & Qiaojie Xiong, 2023. "Nigrostriatal dopamine modulates the striatal-amygdala pathway in auditory fear conditioning," Nature Communications, Nature, vol. 14(1), pages 1-14, 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:nature:v:557:y:2018:i:7704:d:10.1038_s41586-018-0090-6. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.