A central role for denervated tissues in causing nerve sprouting

Brown, M. Christian; Holland, R. L.

doi:10.1038/282724a0

Cited by 118 publications

(50 citation statements)

References 19 publications

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“…One would expect its effect to be equally expressed throughout a fiber, and a mechanism of regulation based on muscle fiber activity would seem to provide the most relevant information; that is, is the terminal successful in evoking activity, and at what level? Moreover, it is well known that directly imposed activity can largely reverse the postsynaptic effects of denervation (Lprmo and Rosenthal, 1972;Drachman and Witzke, 1972;Lprmo et al, 1974;Lemo and Westgaard, 1975;Lomo, 1976;Fambrough, 1979), as well as prevent nerve terminal sprouting (Brown and Holland, 1979;Brown et al, 1980) or innervation by a preimplanted foreign nerve . Synapse elimination is delayed by partial denervation Betz et al, 1980a) and accelerated by nerve stimulation (O'Brien et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

Regulation of synaptic position, size, and strength in anuran skeletal muscle

Nudell¹,

Grinnell²

1983

J. Neurosci.

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An analysis of the physiology, morphology, and position of endplates on identified fibers in the Xenopus laevis pectoralis muscle has revealed the following. 1. The percentage of fibers with one endplate is lower in large muscles, and within the same muscle, singly innervated fibers are smaller than dually innervated fibers.2. Single junctions tend to be stronger than junctions on dually innervated fibers. 3. Single junctions typically are located near the middle of their fibers, while the endplates on dually innervated fibers are located toward either end and usually are separated by at least 20% of the total fiber length. A significant proportion of dually innervated fibers appears to be innervated by the same axon at both junctions.4. Junctions on the same dually innervated fiber tend to be more similar in length than do junctions on different fibers of the same input resistance. This observation is the same whether both junctions on a given fiber are formed by the same or different axons. There is no corresponding tendency for greater similarity in physiological strength of paired junctions, which frequently show large differences in endplate potential amplitude.5. The total terminal length on dually innervated fibers of equivalent input resistance is inversely correlated with the mean release per unit length and total release of both junctions. There is no apparent correlation between the distance separating endplates and their strength or length.The data support a model of synaptic regulation in which nerve terminals are attracted, grow, and are maintained in proportion to the amount of a substance supplied by muscle fibers. Our findings suggest that such a substance is produced or distributed uniformly throughout each fiber in amounts proportional to the fiber size and inversely proportional to the total transmitter output of all junctions innervating the fiber. A form of competitive interaction between the terminals which helps to determine synaptic spacing may involve local depletion or inactivation of this substance.

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Section: Discussionmentioning

confidence: 99%

Regulation of synaptic position, size, and strength in anuran skeletal muscle

Nudell¹,

Grinnell²

1983

J. Neurosci.

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“…Sprouting of nerve terminals is a normal consequence of neu- romuscular inactivity (35,36). Terminals also grow beyond endplate AChR clusters when they re-innervate them following denervation.…”

Section: Retraction Of Terminal Sprouts Upon Re-innervation Of Denervmentioning

confidence: 99%

A Novel Role for Embigin to Promote Sprouting of Motor Nerve Terminals at the Neuromuscular Junction

Lain

Carnejac

Escher

et al. 2009

Journal of Biological Chemistry

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Adult skeletal muscle accepts ectopic innervation by foreign motor axons only after section of its own nerve, suggesting that the formation of new neuromuscular junctions is promoted by muscle denervation. With the aim to identify new proteins involved in neuromuscular junction formation we performed an mRNA differential display on innervated versus denervated adult rat muscles. We identified transcripts encoding embigin, a transmembrane protein of the immunoglobulin superfamily (IgSF) class of cell adhesion molecules to be strongly regulated by the state of innervation. In innervated muscle it is preferentially localized to neuromuscular junctions. Forced overexpression in innervated muscle of a full-length embigin transgene, but not of an embigin fragment lacking the intracellular domain, promotes nerve terminal sprouting and the formation of additional acetylcholine receptor clusters at synaptic sites without affecting terminal Schwann cell number or morphology, and it delays the retraction of terminal sprouts following re-innervation of denervated endplates. Conversely, knockdown of embigin by RNA interference in wild-type muscle accelerates terminal sprout retraction, both by itself and synergistically with deletion of neural cell adhesion molecule. These findings indicate that embigin enhances neural cell adhesion molecule-dependent neuromuscular adhesion and thereby modulates neuromuscular junction formation and plasticity.

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“…All of these conditions that promote sprouting have muscle fiber denervation and/or inactivity in common. Further, the observation that frequency of sprouting in some cases can be significantly reduced by artificially restoring contractility Brown and Holland, 1979;Brown et al, 1980b), coupled with the above results, strongly implicates muscle fiber inactivity as a stimulus to motor neuron sprouting. Despite the considerable evidence that inactive muscle fibers are, directly or indirectly (through subsequent denervation-like muscle fiber changes), a source of some sprouting factor(s) (reviewed by Brown et al, 198 1;Brown, 1984), other interpretations of these and similar results have engendered different hypotheses (e.g., O'Brien et al, 1978;Pestronk and Drachman, 1978).…”

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confidence: 90%

Motor nerve terminal sprouting in formamide-treated inactive amphibian skeletal muscle

Wines

Letinsky

1988

J. Neurosci.

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Motor axons can form sprouts from their terminal arborizations in response to partial denervation, and when exposed to pharmacological blocking agents like TTX, botulinum toxins alpha-bungarotoxin, or curare. Each of these experimental procedures has cessation of muscle contractile activity as a common feature. We tested the specific role of muscle fiber inactivity in regulating nerve terminal sprouting by chronically treating adult frog (Rana pipiens) cutaneous pectoris muscles with formamide. Exposure to formamide, unlike the other compounds used to study sprouting, selectively inhibits muscle contractions without blocking pre- or postsynaptic transmission or muscle fiber action potentials. Repeated formamide applications were used to achieve chronic block of muscle contractile activity in vivo for up to 6 weeks. Motor axons in formamide-treated inactive muscle sprouted only from their terminal arborizations, but not from nodes of Ranvier. The onset of this sprouting was protracted compared with that seen in pharmacologically blocked mammalian muscles, and sprouts in formamide-treated muscles were more complex and ornate. The frequency of sprouting terminals was less in these formamide-treated muscles than that seen after alternate methods of contractile block, and this suggests that contractile inactivity alone serves as only a moderate cue for sprouting. The possibility is discussed that the prolific sprouting seen following neurotoxin administration may, in fact, be due to perturbations in synaptic transmission or muscle electrical activity rather than muscle fiber inactivity.

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A central role for denervated tissues in causing nerve sprouting

Cited by 118 publications

References 19 publications

Regulation of synaptic position, size, and strength in anuran skeletal muscle

Regulation of synaptic position, size, and strength in anuran skeletal muscle

A Novel Role for Embigin to Promote Sprouting of Motor Nerve Terminals at the Neuromuscular Junction

Motor nerve terminal sprouting in formamide-treated inactive amphibian skeletal muscle

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