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Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9

  1. Barbara Commisso
  2. Lingjun Ding
  3. Karl Varadi
  4. Martin Gorges
  5. David Bayer
  6. Tobias M Boeckers
  7. Albert C Ludolph
  8. Jan Kassubek
  9. Oliver Mueller
  10. Francesco Roselli  Is a corresponding author
  1. University of Ulm, Germany
  2. University Hospital Heidelberg, Germany
  3. University of Kiel, Germany
Research Article
  • Cited 2
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Cite this article as: eLife 2018;7:e36892 doi: 10.7554/eLife.36892

Abstract

Amyotrophic Lateral Sclerosis (ALS) is characterized by the progressive degeneration of motoneurons in the primary motor cortex (pMO) and in spinal cord. However, the pathogenic process involves multiple subnetworks in the brain and functional MRI studies demonstrate an increase in functional connectivity in areas connected to pMO despite the ongoing neurodegeneration. The extent and the structural basis of the motor subnetwork remodelling in experimentally-tractable models remain unclear. We have developed a new retrograde AAV9 to quantitatively map the projections to pMO in the SOD1(G93A) ALS mouse model. We show an increase in the number of neurons projecting from somatosensory cortex to pMO at presymptomatic stages, followed by an increase in projections from thalamus, auditory cortex and contralateral MO (inputs from 20 other structures remains unchanged) as disease advances. The stage- and structure-dependent remodeling of projection to pMO in ALS may provide insights into the hyperconnectivity observed in ALS patients.

Article and author information

Author details

  1. Barbara Commisso

    Department of Neurology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Lingjun Ding

    Department of Neurology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Karl Varadi

    Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Martin Gorges

    Department of Neurology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. David Bayer

    Department of Neurology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Tobias M Boeckers

    Department of Anatomy and Cell Biology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Albert C Ludolph

    Department of Neurology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Jan Kassubek

    Department of Neurology, University of Ulm, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Oliver Mueller

    Dept. of Internal Medicine III, University of Kiel, Kiel, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Francesco Roselli

    Department of Neurology, University of Ulm, Ulm, Germany
    For correspondence
    francesco.roselli@uni-ulm.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9935-6899

Funding

Baustein program-Ulm University Medical Faculty

  • Francesco Roselli

Deutsche Forschungsgemeinschaft (GRK1789)

  • David Bayer

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

Ethics

Animal experimentation: All animal experiments have been approved by the Regierungpraesidium Tubingen under the licence no. 1312. All animals were handled according to the federal regulations on animal experimentations and under the supervision of the local veterinary office. Every effort was made to adhere to the 3R guidelines and to minimize suffering.

Human subjects: All subjects included in the human study provided written informed consent according to institutional guidelines; the consent includes the declaration of the understanding of the study design, the agreement to the participation to the study, to the publication of the results, and to the data protection and anonymization procedures (under the chaptes Einwilligungserklaerung"", ""Probandeninformation"", ""Darstellung der Experimente"", ""Datenschutzerklärung""). The study was approved by the Ethics Committee of Ulm University, Ulm, Germany (reference #19/12) and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Reviewing Editor

  1. Moritz Helmstaedter, Max Planck Institute for Brain Research, Germany

Publication history

  1. Received: March 23, 2018
  2. Accepted: August 21, 2018
  3. Accepted Manuscript published: August 23, 2018 (version 1)
  4. Version of Record published: September 5, 2018 (version 2)

Copyright

© 2018, Commisso 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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