You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.

Title: Dynamic neuromuscular remodeling precedes motor-unit loss in a mouse model of ALS}
Article:
Abstract:
Despite being an early event in ALS, it remains unclear whether the denervation of neuromuscular junctions( NMJ) is simply the first manifestation of a globally degenerating motor neuron. Using in vivo imaging of single axons and their NMJs over a three-month period, we identify that single motor-units are dismantled asynchronously in SOD1G37R mice. We reveal that weeks prior to complete axonal degeneration, the dismantling of axonal branches is accompanied by contemporaneous new axonal sprouting resulting in synapse formation onto nearby NMJs. Denervation events tend to propagate from the first lost NMJ, consistent with a contribution of neuromuscular factors extrinsic to motor neurons, with distal branches being more susceptible. These results show that NMJ denervation in ALS is a complex and dynamic process of continuous denervation and new innervation rather than a manifestation of sudden global motor neuron degeneration.
Introduction:
Amyotrophic lateral sclerosis( ALS) is a fatal neurodegenerative disease characterized by upper and lower motor neuron( MN) loss. Loss of neuromuscular junctions( NMJs) is a key pathological event in ALS patients( Fischer et al., 2004; Killian et al., 1994) and in animal models of the disease( Clark et al., 2016; Fischer et al., 2004; Frey et al., 2000; Pun et al., 2006; Tallon et al., 2016). Denervation of NMJs is observed prior to symptom onset( Clark et al., 2016; Fischer et al., 2004; Pun et al., 2006; Tallon et al., 2016; Vinsant et al., 2013) and before any significant MN axonal or cell body loss( Fischer et al., 2004; Vinsant et al., 2013). However, whether early NMJ denervation arises from local branch-specific degeneration( ‘dying-back hypothesis’) or is merely the manifestation of a diseased and globally degenerating motor neuron remains ill-defined. There is considerable evidence which suggests that a subset of degenerating motor-units( MU, a motor neuron and the muscle fibers it innervates) swiftly lose their NMJs while a distinct, yet unaffected, population compensates via axonal sprouting( Pun et al., 2006; Schaefer et al., 2005), somewhat akin to a nerve injury. Indeed, NMJs innervated by fast-fatigable MNs are lost early, followed by fast-fatigue resistant and slow MNs( Frey et al., 2000; Pun et al., 2006). This is further supported by electromyographic( EMG) recordings showing that the number of MUs declines in parallel with muscle strength( Azzouz et al., 1997; Dantes and McComas, 1991; Hegedus et al., 2007; Hegedus et al., 2008; Kennel et al., 1996; McComas et al., 1971) and that surviving MUs increase in size in animal models and in patients( Dantes and McComas, 1991; Dengler et al., 1990; McComas et al., 1971; Schmied et al., 1999). Taken together, these results strongly suggest that the loss of NMJs within a single MU is a dichotomous and mostly synchronous event and that local synaptic events have a limited impact on the denervation process. Under this monotonic paradigm, degenerating MUs are irrevocably caught in a degenerative cascade while surviving MUs attempt to compensate, consequently undermining the relevance of the NMJ as a disease-modifying therapeutic target. However, the rescue of neuronal loss in SOD1 mice does not necessarily improve NMJ denervation( Gould et al., 2006; Parone et al., 2013; Suzuki et al., 2007) suggesting that local branch-specific events may play a key role in NMJ denervation. In ALS, local alterations of synaptic function and molecular signaling take place very early at the NMJ( Arbour et al., 2015; De Winter et al., 2006; Jokic et al., 2006; Rocha et al., 2013; Taetzsch et al., 2017; Tremblay et al., 2017), implying that local, MU-independent, structural changes could occur. Finally, ALS is a non-cell autonomous disease where cell types other than motor neurons contribute to the disease pathogenesis( Boillée et al., 2006a; Ilieva et al., 2009). Contribution of various cell types known to interact with NMJs and motor axons has been suggested( Arbour et al., 2015; Chiu et al., 2009; Keller et al., 2009; Lobsiger et al., 2009; Loeffler et al., 2016; Nardo et al., 2016; Turner et al., 2010; Wang et al., 2012), which could contribute to NMJ loss. In this scenario, asynchronous branch-specific synaptic changes would take place over time within single MUs. Altogether, these divergent paradigms highlight that the precise sequence of events taking place at the NMJ in ALS remains ill-defined. From a therapeutic viewpoint, this distinction is of high importance since it could pinpoint the NMJ as an accessible target that can be exploited within a time window between the onset of structural changes and the global degeneration of the MU, as previously suggested( Cantor et al., 2018; Miyoshi et al., 2017; Pérez-García and Burden, 2012). Here, we used longitudinal repeated in vivo imaging of single motor neuron axonal arbors and their NMJs to directly assess the time course and dynamics of structural changes during ALS progression. We predict that a MU-dependent mechanism would result in the more or less synchronous degeneration of the whole MU over a brief period, while a contribution of local neuromuscular changes would result in the asynchronous loss of NMJs within a single MU.
Discussion:
Overall, this detailed in vivo analysis reveals a previously unsuspected dynamism at the NMJ in an animal model of ALS. Our findings highlight a long temporal window between early branch-specific dismantling and global motor axon degeneration which could be therapeutically exploited in ALS( Arbour et al., 2017; Moloney et al., 2014).
Amyotrophic lateral sclerosis ( ALS ) , also known as Lou Gehrig’s disease , is a fatal neurodegenerative disorder . It occurs when the neurons that control muscles – the motoneurons – disconnect from their target muscles and die . This causes the muscles to weaken and waste away . More and more muscles become affected over time until eventually the muscles that control breathing also become paralyzed . Most patients die within two to five years of diagnosis . Motoneurons consist of a cell body plus a cable-like structure called the axon . The cell body of each motoneuron sits within the spinal cord , and the axon extends out of the spinal cord to the motoneuron’s target muscle . Within the muscle the axon divides into branches , each of which connects with multiple muscle fibers . The breakdown of these connections , known as neuromuscular junctions , is one of the first signs of ALS . Does a motoneuron lose all of its connections with muscle fibers at once , or do the connections break down a few at a time ? This distinction is important as it will help to identify the events that lead to muscle paralysis in ALS . To find out , Martineau et al . studied mice that had two genetic mutations: one that causes ALS and another that produces fluorescent molecules in some motoneurons . This allowed the branches of the motoneurons to be tracked over time with a fluorescence microscope . Martineau et al . found that individual neurons lose their connections to muscle fibers gradually . Moreover , motoneurons grow new branches and form new connections even while losing their old ones . This dual process of pruning and budding lasts for several weeks , until eventually the motoneuron dies . Developing drugs to stabilize neuromuscular junctions during the period when motoneurons gradually disconnect from muscles could be a promising avenue to explore to improve the quality of life of ALS patients . One advantage of this treatment strategy is that neuromuscular junctions in muscles are easier to access than motoneurons inside the spinal cord . To identify potential drugs , future studies will need to focus on the proteins and signals that cause the neuromuscular junctions to break down .