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.

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. Behav Brain Res. 2019 Apr 22;: Authors: Landoni LM, Myles JR, Wells TL, Mayer WP, Akay T Abstract 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 (mSod1G93A 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. We hypothesized that the cholinergic modulation of motor neurons through C-boutons increases motor neuron excitability, and that this C-bouton associated activity increase in surviving motor neurons could compensate for motor unit loss during ALS disease progression. We first provide a thorough analysis of the muscle denervation and behavioral changes in the mSod1G93A mice using immunohistology, electrophysiology, and quantitative analysis of locomotor behavior. Then, in support of our hypothesis, we show that task dependent modulation of hindlimb mu...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research