In ALS pre-symptomatic phase (4–6 weeks old mice), the A2AR-mediated excitation of the neuromuscular transmission had a higher magnitude than that found in age-matched controls, as demonstrated by increases in the mean amplitude and quantal content of EPPs, as well as in the frequency of MEPPs and appearance of giant MEPPs. This evidence concerns the gene ADORA2A and amyotrophic lateral sclerosis.