Amyotrophic Lateral Sclerosis (ALS) is an adult-onset neurodegenerative disease with progressive motor neuron death, where patients usually die within five years of diagnosis. Previously we showed that the C-boutons, which are large cholinergic synapses to motor neurons that modulate motor neuron activity, are necessary for behavioural compensation in mSOD1G93A mice, a mouse model for ALS. We reasoned that, since the C-boutons likely increase the excitability of surviving motor neurons to compensate for motor neuron loss during ALS disease progression, then amplitude modulation through the C-boutons likely increases motor neuron stress and worsens disease progression. By comparing male and female mSOD1G93A mice to mSOD1G93A mice with genetically silenced C-boutons (mSOD1G93A; Dbx1::cre; ChATfl/fl) (mSOD1G93A/Coff), we show that the C-boutons do not influence the humane endpoint of mSOD1G93A mice; however, our histological analysis shows that C-bouton silencing significantly improves fast twitch muscle inne...