The effects of electrical inactivity and denervation on the distribution of acetylcholine receptors in developing rat muscle

Ziskind-Conhaim, Lea; Bennett, Jeffrey I.

doi:10.1016/0012-1606(82)90224-x

Cited by 38 publications

(16 citation statements)

References 36 publications

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“…While fetal myofibers do show evidence of extrajunctional receptors, these receptors are not found organized into clusters. However, extrajunctional clusters are produced by embryonic rat myotubes in vivo after denervation or treatment with tetrodotoxin to prevent nerve-evoked muscle activity (Braithwaite and Harris, 1979;Slater, 1982;Ziskind-Conhaim and Bennett, 1982). Under these conditions, nu- merous extrajunctional clusters appear, approximately 5-22 pm in size, comparable to those seen in the present study.…”

Section: Extrajunctional Achr Clusterssupporting

confidence: 82%

The clustering of acetylcholine receptors and formation of neuromuscular junctions in regenerating mammalian muscle grafts

Womble

Carlson

1986

Am. J. Anat.

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The present investigation was undertaken to study the relationship between acetylcholine receptor (AchR) clustering and endplate formation within regenerating skeletal muscle grafts. Silver staining of nerves was combined with rhodamine-alpha-bungarotoxin labeling of AchR clusters in heterotopic grafts of the rat soleus muscle. Two major graft procedures were used: whole muscle grafts and grafts which lacked the zone of original motor endplates (MEP-less grafts). These categories were subdivided into standard grafts, where subsequent innervation was allowed, and noninnervated grafts, which were experimentally deprived of innervation. Grafting brought about the death and removal of muscle fibers, followed by regeneration of myotubes within surviving basal lamina sheaths. A transient population of small extra-junctional AchR clusters spontaneously appears shortly after myotube formation in all four muscle graft types. Early myotubes of whole muscle grafts (both innervated and standard grafts, prior to the time of innervation) also develop presumptive secondary synaptic clefts and large, organized aggregations of AchRs at original synaptic sites. At later times, nerves regenerating into standard whole muscle and MEP-less grafts lead to the formation of numerous ectopic endplates. In whole muscle grafts, endplates may also form at original synaptic sites. Functional graft innervation is achieved in whole muscle and MEP-less grafts as early as 20 days postgrafting. The results of this study support the existence of still-unknown factors associated with the original synaptic site which can direct postsynaptic differentiation independent of innervation. They also demonstrate that functional endplates may form in mammalian muscle grafts at both original synaptic sites and ectopic locations, thus indicating that the zone of original synaptic sites is not necessary for the establishment of numerous functional and morphologically well-differentiated endplates.

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Section: Extrajunctional Achr Clusterssupporting

confidence: 82%

The clustering of acetylcholine receptors and formation of neuromuscular junctions in regenerating mammalian muscle grafts

Womble

Carlson

1986

Am. J. Anat.

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“…In mouse aneural muscle fibers, ACh receptors (AChRs) are initially evenly distributed and subsequently accumulate in the middle, where innervation occurs; this happens, for example, between embryonic day 12.5 (E12.5) and E13.5 in the diaphragm (Bevan and Steinbach, 1977;Braithwaite and Harris, 1979;Creazzo and Sohal, 1983;Ziskind-Conhaim and Bennett, 1982). In vitro studies of synapse formation indicated, however, that spinal neuron axons ignore such pre-existing, primitive AChR clusters on co-cultured muscle fibers and instead form synapses at new locations (Anderson and Cohen, 1977), which indicates a dominant role for motoneurons in determining where NMJs are formed.…”

Section: A Chicken-and-egg Problem: Motoneurons and Muscle Fibersmentioning

confidence: 99%

To build a synapse: signaling pathways in neuromuscular junction assembly

2010

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SummarySynapses, as fundamental units of the neural circuitry, enable complex behaviors. The neuromuscular junction (NMJ) is a synapse type that forms between motoneurons and skeletal muscle fibers and that exhibits a high degree of subcellular specialization. Aided by genetic techniques and suitable animal models, studies in the past decade have brought significant progress in identifying NMJ components and assembly mechanisms. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues, which shed light on synaptogenesis in the brain and contribute to a better understanding of muscular dystrophy. Key words: Neural development, Neuromuscular junction, Retrograde signaling, Synapse formation IntroductionThe brain contains billions of nerve cells, or neurons, which receive and integrate signals from the environment, and which govern the body's responses. Nervous system activity is made possible by synapses, contacts formed either between neurons or between a neuron and a target cell. Synapses are asymmetric structures in which neurotransmitter molecules are released from the presynaptic membrane and activate receptors on the postsynaptic membrane, thus establishing neuronal communication. As such, synapses are fundamental units of neural circuitry and enable complex behaviors. The neuromuscular junction (NMJ) is a type of synapse formed between motoneurons and skeletal muscle fibers. Large and easily accessed experimentally, this peripheral synapse has contributed greatly to the understanding of the general principles of synaptogenesis and to the development of potential therapeutic strategies for muscular disorders. The NMJ uses different neurotransmitters in different species; for example, acetylcholine (ACh) in vertebrates and glutamate in Drosophila, both of which are excitatory and cause muscle contraction. In Caenorhabditis elegans, there are two types of NMJs: at excitatory NMJs, ACh causes muscle contraction, whereas inhibitory NMJs release g-aminobutyric acid (GABA) to cause muscle relaxation. Motor nerve terminals differentiate to form presynaptic active zones, where synaptic vesicles dock and release neurotransmitters. On the apposed postsynaptic membranes, neurotransmitter receptors are packed at high densities. Aided by genetic techniques and by the use of suitable animal models, including rodents, zebrafish, Drosophila and C. elegans, studies in the past decade have brought significant progress, not only in identifying components present in pre-and postsynaptic membranes, but also in understanding the mechanisms that underpin NMJ assembly. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues from motor nerves and muscle fibers. Readers are referred to other outstanding reviews for a broad view of NMJ development (see Froehner, 1993;Hall and Sanes, 1993;Kummer et al., 2006;Salpeter and Loring, 1985;Schaeffer et al., 2001). NMJ formati...

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“…We defined a synapse with immunostaining as the apposition of a presynaptic SV2 ( a synaptic vesicle antigen) containing profile with a postsynaptic acetylcholine ( ACh ) receptor cluster visualized with rhodamine aBTX. It was important to have markers for both pre-and postsynaptic elements since some earlier studies had relied on only postsynaptic markers (i.e., ACh receptor clusters or sites of AChE) to define innervation density, and in at least some cases these extra "synapses" induced by activity blockade were found to be devoid of presynaptic elements ( Ziskind-Conhaim and Bennett, 1982). It is also not possible at these early stages to define synapses ultrastructurally with any confidence.…”

Section: Intramuscular Nerve Branching and Synapse Formation During Nmentioning

confidence: 99%

The relationship of intramuscular nerve branching and synaptogenesis to motoneuron survival

Landmesser

1992

J. Neurobiol.

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The target has been considered for some time to play a major role in allowing neurons to survive the period of naturally occurring cell death. For the motoneurons that innervate the chick limb, evidence is presented that suggests access to target-derived trophic factor via intramuscular nerve branches and synapses may be important in regulating neuronal survival. Alterations in branching and synapse formation produced by activity blockade as well as by alteration of adhesion molecule function are shown to result in changes in motoneuron survival consistent with the proposed hypothesis. The relevance of these observations to the numerical-matching hypothesis of vertebrate neuronal cell death is also considered.

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The effects of electrical inactivity and denervation on the distribution of acetylcholine receptors in developing rat muscle

Cited by 38 publications

References 36 publications

The clustering of acetylcholine receptors and formation of neuromuscular junctions in regenerating mammalian muscle grafts

The clustering of acetylcholine receptors and formation of neuromuscular junctions in regenerating mammalian muscle grafts

To build a synapse: signaling pathways in neuromuscular junction assembly

The relationship of intramuscular nerve branching and synaptogenesis to motoneuron survival

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