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

eLife

Tobias M Boeckers¹  Karl Varadi²  Oliver J Müller³  Albert C Ludolph⁴  Martin Gorges⁴  Barbara Commisso⁴  Francesco Roselli⁴  Jan Kassubek⁴  David Bayer⁴  Lingjun Ding⁴ 

[1] Department of Anatomy and Cell biology, University of Ulm, Ulm, Germany;Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany;Department of Internal Medicine, University of Kiel, Kiel, Germany;Department of Neurology, University of Ulm, Ulm, Germany;

关键词: amyotrophic lateral sclerosis;    primary motor cortex;    AAV9;    retrograde tracing;   

DOI  :  10.7554/eLife.36892

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown