Locomotor deficits in a mouse model of ALS are paralleled by loss of V1-interneuron connections onto fast motor neurons

Ilary Allodi*, Roser Montañana-Rosell, Raghavendra Selvan, Peter Löw, Ole Kiehn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Downloads (Pure)


ALS is characterized by progressive inability to execute movements. Motor neurons innervating fast-twitch muscle-fibers preferentially degenerate. The reason for this differential vulnerability and its consequences on motor output is not known. Here, we uncover that fast motor neurons receive stronger inhibitory synaptic inputs than slow motor neurons, and disease progression in the SOD1G93A mouse model leads to specific loss of inhibitory synapses onto fast motor neurons. Inhibitory V1 interneurons show similar innervation pattern and loss of synapses. Moreover, from postnatal day 63, there is a loss of V1 interneurons in the SOD1G93A mouse. The V1 interneuron degeneration appears before motor neuron death and is paralleled by the development of a specific locomotor deficit affecting speed and limb coordination. This distinct ALS-induced locomotor deficit is phenocopied in wild-type mice but not in SOD1G93A mice after appearing of the locomotor phenotype when V1 spinal interneurons are silenced. Our study identifies a potential source of non-autonomous motor neuronal vulnerability in ALS and links ALS-induced changes in locomotor phenotype to inhibitory V1-interneurons.

Original languageEnglish
Article number3251
Number of pages18
JournalNature Communications
Publication statusPublished - 31 May 2021


  • Amyotrophic Lateral Sclerosis (ALS)/genetics
  • Animals
  • Disease Models, Animal
  • Female
  • Homeodomain Proteins/metabolism
  • Humans
  • Interneurons/pathology
  • Locomotion/physiology
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Neurons/pathology
  • Muscle Fibers, Fast-Twitch/physiology
  • Neuromuscular Junction/pathology
  • Spinal Cord/cytology
  • Superoxide Dismutase/genetics
  • Superoxide Dismutase-1/genetics


Dive into the research topics of 'Locomotor deficits in a mouse model of ALS are paralleled by loss of V1-interneuron connections onto fast motor neurons'. Together they form a unique fingerprint.

Cite this