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

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 connec...

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Hauptverfasser: Commisso, Barbara (VerfasserIn) , Ding, Lingjun (VerfasserIn) , Varadi, Karl (VerfasserIn) , Gorges, Martin (VerfasserIn) , Bayer, David (VerfasserIn) , Boeckers, Tobias M (VerfasserIn) , Ludolph, Albert C. (VerfasserIn) , Kassubek, Jan Rainer (VerfasserIn) , Müller, Oliver J. (VerfasserIn) , Roselli, Francesco (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: Aug 23, 2018
In: eLife
Year: 2018, Jahrgang: 7
ISSN:2050-084X
DOI:10.7554/eLife.36892
Online-Zugang:Verlag, Volltext: https://doi.org/10.7554/eLife.36892
Volltext
Verfasserangaben:Barbara Commisso, Lingjun Ding, Karl Varadi, Martin Gorges, David Bayer, Tobias M Boeckers, Albert C Ludolph, Jan Kassubek, Oliver J Müller, Francesco Roselli
Beschreibung
Zusammenfassung: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 remodeling 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.
Beschreibung:Gesehen am 12.06.2019
Beschreibung:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.36892

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