Maximizing the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials.

Mouse models of amyotrophic lateral sclerosis (ALS) enable testing of novel therapeutic interventions. However, treatments that have extended survival in mice have often failed to translate into human benefit in clinical trials. Compound muscle action potentials (CMAPs) are a simple neurophysiological test that measures the summation of muscle fiber depolarization in response to maximal stimulation of the innervating nerve.

Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons in the central nervous system (CNS). Mutations in the metalloenzyme SOD1 are associated with inherited forms of ALS and cause a toxic gain of function thought to be mediated by dimer destabilization and misfolding. SOD1 binds two Cu and two Zn ions in its homodimeric form.

Cholinergic modulation of motor neurons through the C-boutons are necessary for the locomotor compensation for severe motor neuron loss during amyotrophic lateral sclerosis disease progression.

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by progressive motor neuron (MN) death that leads to muscle weakness, paralysis, and eventually death. When symptoms become clinically evident, patients and ALS model animals (mSod1 mice) have already lost a large portion of motor units, suggesting the existence of a compensatory mechanism that allows for reactively normal movement despite denervation. Furthermore, it has been shown that specialized cholinergic synapses, the C-boutons, regulate activity strength of motor output in a task dependent manner.

Modular organization of murine locomotor pattern in the presence and absence of sensory feedback from muscle spindles.

Key Points: Locomotion on land and in water requires the coordination of a great number of muscle activations and joint movements. Constant feedback about the position of own body parts in relation to the surrounding environment and the body itself (proprioception) is required to maintain stability and avoid failure. The central nervous system may follow a modular type of organization by controlling muscles in orchestrated groups (muscle synergies) rather than individually.