Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disease affecting motor neurons. Glial dysfunction is a hallmark of ALS, contributing to numerous aspects of the disease. Although loss of neuromuscular junction (NMJ) is an early event, it remains unclear whether it is a consequence of local pathological signals or the expression of a degenerating neuron. Indeed, the rescue of motor neuron death does not necessarily rescue NMJ loss, suggesting that the local synaptic and glial mechanisms may play a key role. Particularly, perisynaptic Schwann cells (PSCs), glial cells at the NMJ, regulate the synaptic and structural plasticity of this synapse and may be implicated in the disease. Hence, we hypothesized that local branch-specific NMJ loss would precede the global degeneration of motor neurons (motor-unit degeneration) and that PSCs would show maladapted properties in ALS. First, we sought to directly assess the time course of structural changes in the axonal arborization of individual motor neurons using repeated in vivo imaging in a slow progressing model of ALS (SOD1^G37R mice). We found that individual axonal branches and synapses are dismantled asynchronously for weeks before the whole motor axon degenerates. Surprisingly, we observed that the dismantling of individual axonal branches was accompanied by contemporaneous axonal sprouting and synapse formation onto nearby NMJs. Axonal arborizations, but not axon terminals, sprouted almost exclusively onto NMJs that they did not initially innervate, thus increasing motor-unit size. Paradoxically, motor-units failed to re-innervate their dismantled NMJs which suggests that reinnervation mechanisms are abnormal in ALS. These results support a model in which NMJ denervation in ALS is a dynamic process of continuous denervation and maladapted new innervation. Next, we sought to investigate whether PSC properties were altered during ALS progression knowing their role in regulating NMJ stability and reinnervation. Using Ca²⁺-imaging, we found that PSCs displayed an increased muscarinic receptor (mAChR)-dependent activity. Glial mAChRs are known to regulate the gene expression of PSCs and their ability to favor reinnervation. Hence, we sought to analyze PSC-dependent NMJ repair mechanisms in symptomatic SOD1^G37R mice. We found that PSCs extended disorganized processes from denervated NMJs and failed to initiate or guide nerve terminal sprouts, consistent with our in-vivo observations. We also found that PSCs failed to upregulate Galectin-3 (MAC-2) in SOD1 mice, a marker of glial phagocytosis, which is incompatible with their role as axonal debris phagocytes. Altogether, these results show that denervation of NMJs is a dynamic local process to which glial cells exert a maladapted response. This raises stabilization of NMJs or enhancement of re-innervation through glial mechanisms as attractive therapeutic targets for ALS.