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What is the true discharge rate and pattern of the striatal projection neurons in Parkinson's disease and Dystonia?

  1. Dan Valsky
  2. Shai Heiman Grosberg
  3. Zvi Israel
  4. Thomas Boraud
  5. Hagai Bergman
  6. Marc Deffains  Is a corresponding author
  1. The Hebrew University - Hadassah Medical School, Israel
  2. Hadassah University Hospital, Israel
  3. University of Bordeaux, France
Research Article
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Cite this article as: eLife 2020;9:e57445 doi: 10.7554/eLife.57445

Abstract

Dopamine and striatal dysfunctions play a key role in the pathophysiology of Parkinson's disease (PD) and Dystonia, but our understanding of the changes in the discharge rate and pattern of striatal projection neurons (SPNs) remains limited. Here, we recorded and examined multi-unit signals from the striatum of PD and dystonic patients undergoing deep brain stimulation surgeries. Contrary to earlier human findings, we found no drastic changes in the spontaneous discharge of the well-isolated and stationary SPNs of the PD patients compared to the dystonic patients or to the normal levels of striatal activity reported in healthy animals. Moreover, cluster analysis using SPN discharge properties did not characterize two well-separated SPN subpopulations, indicating no SPN subpopulation-specific (D1 or D2 SPNs) discharge alterations in the pathological state. Our results imply that small to moderate changes in spontaneous SPN discharge related to PD and Dystonia are likely amplified by basal ganglia downstream structures.

Article and author information

Author details

  1. Dan Valsky

    Department of Medical Neurobiology, The Hebrew University - Hadassah Medical School, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.

  2. Shai Heiman Grosberg

    Department of Medical Neurobiology, The Hebrew University - Hadassah Medical School, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.

  3. Zvi Israel

    Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.

  4. Thomas Boraud

    IMN, University of Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.

  5. Hagai Bergman

    Department of Medical Neurobiology, The Hebrew University - Hadassah Medical School, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2402-6673

  6. Marc Deffains

    IMN, University of Bordeaux, Bordeaux, France
    For correspondence
    marc.deffains@u-bordeaux.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0734-6541

Funding

European Research Council

  • Hagai Bergman

Rosetrees

  • Hagai Bergman

Israel Science Foundation

  • Hagai Bergman

Israel Authority for Innovation

  • Hagai Bergman

French National Research Agency

  • Marc Deffains

French National Center for Scientific Research

  • Marc Deffains

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All patients met the criteria for DBS and signed a written informed consent for surgery that involved microelectrode recording. This study was authorized and approved by the Institutional Review Board of Hadassah Hospital in accordance with the Helsinki Declaration (reference code: 0168-10-HMO)

Reviewing Editor

  1. Aryn H Gittis, Carnegie Mellon University, United States

Publication history

  1. Received: March 31, 2020
  2. Accepted: August 14, 2020
  3. Accepted Manuscript published: August 19, 2020 (version 1)
  4. Version of Record published: September 1, 2020 (version 2)

Copyright

© 2020, Valsky et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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    Background: Fatal Familial Insomnia (FFI) is a genetic prion disease caused by the D178N mutation in the prion protein gene (PRNP) in coupling phase with methionine at PRNP 129. In 2017, we have shown that the olfactory mucosa (OM) collected from FFI patients contained traces of PrPSc detectable by Protein Misfolding Cyclic Amplification (PMCA).

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