Remodelling of the neuromuscular junction after subtotal disuse (original) (raw)

Lack of motor recovery after prolonged denervation of the neuromuscular junction is not due to regenerative failure

The European journal of neuroscience, 2015

Motor axons in peripheral nerves have the capacity to regenerate after injury. However, full functional motor recovery rarely occurs clinically, and this depends on the nature and location of the injury. Recent preclinical findings suggest that there may be a time after nerve injury where, while regrowth to the muscle successfully occurs, there is nevertheless a failure to re-establish motor function, suggesting a possible critical period for synapse reformation. We have now examined the temporal and anatomical determinants for the re-establishment of motor function after prolonged neuromuscular junction (NMJ) denervation in rats and mice. Using both sciatic transection-resuture and multiple nerve crush models in rats and mice to produce prolonged delays in reinnervation, we show that regenerating fibres reach motor endplates and anatomically fully reform the NMJ even after extended periods of denervation. However, in spite of this remarkably successful anatomical regeneration, afte...

Maturation and Maintenance of the Neuromuscular Synapse

Neuron, 2000

Dystrophin was identified as the cytoskeletal protein product of the gene mutated in Duchenne and Becker muscular dystrophies . Subsequently, dystrophin was shown to be a major component of a multimolecular membrane-associated complex, the ). The DGC includes dystrophin or its homolog, utrophin; three groups of St. Louis, Missouri 63110 ‡ Howard Hughes Medical Institute transmembrane proteins (dystroglycans [DGs], sarcoglycans, and sarcospan); and two groups of soluble pro-Departments of Physiology and Biophysics and of Neurology teins, the dystrobrevins and syntrophins. The DGC links the cytoskeleton to the extracellular matrix; cytoskeletal University of Iowa College of Medicine Iowa City, Iowa 52242 actin binds to dystrophin, which binds to ␤-DG in the membrane, and the extracellular domain of ␤-DG interacts with ␣-DG, which in turn binds to laminin ␣2 in the basal lamina. This complex is required for muscle stability, Summary as demonstrated by the findings that mutations in dystrophin, laminin ␣2, or any of four sarcoglycan genes all The dystrophin-glycoprotein complex (DGC) links the lead to muscular dystrophies (reviewed by Tinsley et al., cytoskeleton of muscle fibers to their extracellular ma-1994; Straub and Campbell, 1997; Ozawa et al., 1998).

Differential muscle-driven synaptic remodeling in the neuromuscular junction after denervation

2010

We used knock-in mice that express green fluorescent protein (GFP)-labeled embryonic-type acetylcholine receptors to investigate postsynaptic responses to denervation of fast-twitch and slow-twitch muscle fibers, and to visualize the integration of newly synthesized GFP-labeled embryonic-type receptors into adult synapses. The embryonic-type receptors are transiently expressed and incorporated into the denervated endplates. They replaced synaptic adult-type receptors in a directed fashion, starting from the endplate's periphery and proceeding to its central regions. The progress of embryonic-type receptor expression with respect to transcriptional control is a transient, short-term activation mechanism. The less pronounced increase in the expression levels of the GFP-labeled receptors revealed a differential shift in the integration and degradation processes that constitute the dynamic equilibrium of the synaptic receptor pool. Therefore, we were able to model the changes in the total receptor load of the neuromuscular endplate following denervation as a function of the abundance of available receptors and the initial receptor load of the endplate.

Synapse formation and elimination: Role of activity studied in different models of adult muscle reinnervation

Journal of Neuroscience Research, 2007

Synapse competition and elimination are a general developmental process both in central and in peripheral nervous systems that is strongly activity dependent. Some common features regulate synapse competition, and one of these is an application to development of the Hebb's postulate of learning: repeated coincident spike activity in competing presynaptic inputs on the same target cell inhibits competition, whereas noncoincident activity promotes weakening of some of the inputs and ultimately their elimination. Here we report experiments that indicate that the development of muscle innervation (initial polyneuronal innervation and subsequent synapse elimination) follows the Hebb's paradigm. We utilized two different models of muscle reinnervation in the adult rat: 1) we crushed nerves going to soleus or extensor digitorum longus muscles, to activate regeneration of the presynaptic component of the neuromuscular junctions (NMJ), or 2) we injected the soleus muscle with Marcaine (a myotoxic agent) to activate regeneration of the postsynaptic component, the muscle fiber. A condition of transient polyneuronal innervation occurs during NMJ regeneration in both cases, although the two models differ insofar as the relative strength of the competing inputs is concerned. During the period of competition (a few days or weeks, in Marcaine or crush experiments, respectively), we imposed a synchronous firing pattern on the competing inputs by stimulating motor axons distal to a chronic conduction block and demonstrated that this procedure strongly inhibits synapse elimination, with respect to control muscles in which regeneration occurs under natural impulse activity of motoneurons. V V C 2006 Wiley-Liss, Inc.

The effect of lengthening contractions on neuromuscular junction structure in adult and old mice

Age (Dordrecht, Netherlands), 2016

Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days ...

Factors that influence regeneration of the neuromuscular junction

Journal of Experimental Biology

Regeneration of neuromuscular junctions after trauma occurs in an orderly way and relies on communication between nerve and muscle. This paper summarizes evidence that factors which direct the growth and differentiation of both pre- and postsynaptic components of regenerating neuromuscular junctions are associated with the extracellular matrix of muscles.