Abstract
This review considers the relative roles of sprouting stimuli, perisynaptic Schwann cells and neuromuscular activity in axonal sprouting at the neuromuscular junction in partially denervated muscles. A number of sprouting stimuli, including insulin-like growth factor II, which are generated from inactive muscle fibers in partially denervated and paralyzed skeletal muscles, has been considered. There is also evidence that perisynaptic Schwann cells induce and guide axonal sprouting in adult partially denervated muscles. Excessive neuromuscular activity significantly reduces bridging of perisynaptic Schwann cell processes between innervated and denervated endplates and thereby inhibits axonal sprouting in partially denervated adult muscles. Elimination of neuromuscular activity is also detrimental to sprouting in these muscles, suggesting that calcium influx into the nerve is crucial for axonal sprouting. The role of neuromuscular activity in axonal sprouting will be considered critically in the context of the roles of sprouting stimuli and perisynaptic Schwann cells in the process of axonal sprouting.
Similar content being viewed by others
References
ASTROW, S. H., SON, Y. J. & THOMPSON, W. J. (1994) Differential neural regulation of a neuromuscular junction-associated antigen in muscle fibers and Schwann cells. The Journal of Neurobiology 25, 93–952.
BROMBERG, M. B., FORSHEW, D. A., NAU, K. L., BROMBERG, J., SIMMONS, Z. & FRIES, T. J. (1993) Motor unit number estimation, isometric strength, and electromyographic measures in amyotrophic lateral sclerosis. Muscle & Nerve 16, 121–1219.
BROWN, M. C., GOODWIN, G. M. & IRONTON, R. (1977) Prevention of motor nerve sprouting in botulinum toxin poisoned mouse soleus muscles by direct stimulation of the muscle. The Journal of Physiology (London) 267, 42P-43P.
BROWN, M. C. & HOLLAND, R. L. (1979) A central role for denervated tissues in causing nerve sprouting. Nature 282, 72–726.
BROWN, M. C., HOLLAND, R. L. & HOPKINS, W. G. (1981) Motor nerve sprouting. Annual Review of Neuroscience 4, 1–42.
BROWN, M. C., HOLLAND, R. L., HOPKINS, W. G. & KEYNES, R. J. (1980a) Anassessment of the spread of the signal for terminal sprouting within and between muscles. Brain Research 210, 14–151.
BROWN, M. C., HOLLAND, R. L. & IRONTON, R. (1978a) Degenerating nerve products affect innervated muscle fibres. Nature 275, 65–654.
BROWN, M. C., HOLLAND, R. L. & IRONTON, R. (1978b) Is the stimulus for motoneurone terminal sprouting localized? The Journal of Physiology 282, – 8P.
BROWN, M. C., HOLLAND, R. L. & IRONTON, R. (1980b) Nodal and terminal sprouting frommotor nerves in fast and slow muscles of the mouse. The Journal of Physiology 306, 49–510.
BROWN, M. C. & IRONTON, R. (1977) Motor neurone sprouting induced by prolonged tetrodotoxin block of nerve action potential. Nature 265, 45–461.
BROWN, M. C. & IRONTON, R. (1978) Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles. The Journal of Physiology 278, 32–348.
CARONI, P. & GRANDES, P. (1990) Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors. The Journal of Cell Biology 110, 130–1317.
CARONI, P., SCHNEIDER, C., KIEFER, M. C. & ZAPF, J. (1994) Role of muscle insulin-like growth factors in nerve sprouting: Suppression of terminal sprouting in paralyzed muscle by IGF-binding protein 4. The Journal of Cell Biology 125, 89–902.
COHAN, C. S., CONNOR, J. A. & KATER, S. B. (1987) Electrically and chemically mediated increases in intracellular calcium in neuronal growth cones. The Journal of Neuroscience 7, 358–3699.
COLLINS, F., SCHMIDT, M. F., GUTHRIE, P. B. & KATER, S. B. (1991) Sustained increase in intracellular calcium promotes neuronal survival. The Journal of Neuroscience 11, 258–2587.
CONNOLD, A. L. & VRBOVÁ, G. (1990) The effect ofmuscle activity on motor unit size in partially denervated rat soleus muscles. Neuroscience 34, 52–532.
CONNOLD, A. L. & VRBOVÁ, G. (1991) Temporary loss of activity prevents the increase of motor unit size in partially denervated rat soleus muscles. The Journal of Physiology 434, 10–119.
CONNOR, J. A., KATER, S. B., COHAN, C. & FINK, L. (1990) Ca2+ dynamics in neuronal growth cones: Regulation and changing patterns of Ca2+ entry. Cell Calcium 11, 23–239.
DENGLER, R., KONSTANZER, A., KUTHER, G., HESSE, S., WOLF, W. & STRUPPLER, A. (1990) Amyotrophic lateral sclerosis: Macro-EMG and twitch forces of singlemotor units. Muscle & Nerve 13, 54–550.
EINSIEDEL, L. J. & LUFF, A. R. (1994) Activity and motor unit size in partially denervated rat medial gastrocnemius. The Journal of Applied Physiology 76, 266–2671.
FISHER, T. J., VRBOVA, G. & WIJETUNGE, A. (1989) Partial denervation of the rat soleus muscle at two different developmental stages. Neuroscience 28, 75–763.
FU, S. Y. & GORDON, T. (1997) The cellular and molecular basis of peripheral nerve regeneration. Molecular Neurobiology 14, 6–116.
GARDINER, P. F. & FALTUS, R. E. (1986) Contractile responses of rat plantaris muscles following partial denervation, and the influence of daily exercise. Pflugers Archiv 406, 5–56.
GARDINER, P. F., MICHEL, R. N. & IADELUCA, G. (1984) Previous exercise training influences functional sprouting of rat hindlimb motoneurons in response to partially denervation. Neuroscience Letters 45, 12–127.
GEORGIOU, J., ROBITAILLE, R. & CHARLTON, M. P. (1999) Muscarinic control of cytoskeleton in perisynaptic glia. The Journal of Neuroscience 19, 383–3846.
GLAZNER, G. W. & ISHII, D. N. (1995) Insulin like growth factor gene expression in rat muscle during reinnervation. Muscle & Nerve 18, 143–1442.
GLAZNER, G. W., MORRISON, A. E. & ISHII, D. N. (1994) Elevated insulin-like growth factor (IGF) gene expression in sciatic nerves during IGF-supported nerve regeneration. Molecular Brain Research 25, 26–272.
GORDON, T. & PATTULLO, M. C. (1993) Plasticity of muscle fiber and motor unit types. Exercise and Sport Sciences Rev 21, 33–362.
GRIMBY, G., EINARSSON, G., HEDBERG, M. & ANIANSSON, A. (1989) Muscle adaptive changes in postpolio subjects. Scandinavian Journal of Rehabilitation Medicine 21, 1–26.
GURNEY, M. E. (1984) Suppression of sprouting at the neuromuscular junction by immune sera. Nature 307, 54–548.
GURNEY, M. E., APATOFF, B. R. & HEINRICH, S. P. (1986) Suppression of terminal axonal sprouting at the neuromuscular junction by monoclonal antibodies against a muscle-derived antigen of 56,000 daltons. The Journal of Cell Biology 102, 226–2272.
HALL, Z. W. & SANES, J. R. (1993) Synaptic structure and development: The neuromuscular junction. Neuron 10, 9– 121.
HALSTEAD, L. S. (1998) Post-polio syndrome. Scientific American 278, 4–47.
HALSTEAD, L. S. & GRIMBY, G. (1995) Post-Polio Syndrome. Philadelphia: Hanley and Belfus, Inc.
HALSTEAD, L. S. & WIECHERS, D. O. (1987) Research and Clinical Aspects of the Late Effects of Poliomyelitis. White Plains, New York: March of Dimes Birth Defects Foundation.
HENDERSON, C. E., HUCHET, M. & CHANGEUX, J. P. (1983) Denervation increases a neurite-promoting activity in extracts of skeletal muscle. Nature 302, 60–611.
HENNEMAN, E. & MENDELL, L. M. (1981) Functional organization of the motoneurone pool and its inputs. In Handbook of Physiology. The Nervous System. Motor Control. pp. 34–442.Washington, DC: American Physiology Society.
HOFFMAN, H. (1950) Local reinnervation in partially denervatedmuscles: Ahistophysiological study. Australian Journal of Experimental Biology and Medical Science 28, 38–397.
HOLLAND, R. L. & BROWN, M. C. (1980) Postsynaptic transmission block can cause terminal sprouting of a motor nerve. Science 207, 64–651.
JAHROMI, B. S., ROBITAILLE, R. & CHARLTON, M. P. (1992) Transmitter release increases intracellular calcium in perisynaptic Schwann cells in situ. Neuron 8, 106– 1077.
JANSEN, J. K. & FLADBY, T. (1990) The perinatal reorganization of the innervation of skeletal muscle in mammals. Progress in Neurobiology 34, 3–90.
KATER, S. B., MATTSON, M. P., COHAN, C. S. & CONNOR, J. A. (1988) Calcium regulation of the neuronal growth cone. Trends in Neuroscience 11, 31–320.
KATER, S. B., MATTSON, M. P. & GUTHRIE, P. B. (1989) Calcium-induced neuronal degeneration: A normal growth cone regulating signal gone away. Annals of The New York Academy of Sciences 568, 25–261.
KATER, S. B. & MILLS, L. R. (1991) Regulation of growth cone behavior by calcium. The Journal of Neuroscience 11, 89–899.
KO, C. P. & CHEN, L. (1996) Synaptic remodeling revealed by repeated in vivo observations and electron microscopy of identified frog neuromuscular junctions. J. Neurosci. 16, 178–1790.
KOIRALA, S., QIANG, H. & KO, C. P. (2000) Reciprocal interactions between perisynaptic Schwann cells and regenerating nerve terminals at the frog neuromuscular junction. J. Neurobiol. 44, 34–360.
LOVE, F. M., SON, Y. J. & THOMPSON, W. J. (2003) Activity alters muscle reinnervation and terminal sprouting by reducing the number of Schwann cell pathways that grow to link synaptic sites. The Journal of Neurobiology 54, 56–576.
LOVE, F. M. & THOMPSON, W. J. (1999) Glial cells promote muscle reinnervation by responding to activitydependent postsynaptic signals. The Journal of Neuroscience 19, 1039–10396.
LUFF, A. R., HATCHER, D. D. & TORKKO, K. (1988) Enlarged motor units resulting from partial denervation of cat hindlimb muscles. The Journal of Neurophysiology 59, 137–1394.
MATTSON, M. P. & KATER, S. B. (1987) Calcium regulation of neurite elongation and growth cone motility. The Journal of Neuroscience 7, 403–4042.
MATTSON, M. P., TAYLOR-HUNTER, A. & KATER, S. B. (1988) Neurite outgrowth in individual neurons of a neuronal population is differentially regulated by calcium and cyclic AMP. The Journal of Neuroscience 8, 170–1711.
MICHEL, R. N. & GARDINER, P. F. (1989) Influence of overload on recovery of rat plantaris from partial denervation. The Journal of Applied Physiology 66, 73–740.
MILNER-BROWN, H. S., STEIN, R. B. & LEE, R. G. (1974) Contractile and electrical properties of human motor units in neuropathies and motor neurone disease. The Journal of Neurology, Neurosurgery and Psychiatry 37, 67–676.
NISHIMUNE, H., UYEDA, A., NOGAWA, M., FUJIMOTO, H., FUJIMORI, K. E. & TAGUCHI, T. (1997) Neurocrescin: A neurite-outgrowth factor secreted by muscle in a activity dependent manner. Society for Neuroscience Abstract 23, 244.2.
PACHTER, B. R. & EBERSTEIN, A. (1992) Long-term effects of partial denervation on sprouting and muscle fiber area in rat plantaris. Experimental Neurology 116, 24–255.
PAMPHLETT, R. (1989) Early terminal and nodal sprouting of motor axons after botulinum toxin. The Journal of Neuroscience 92, 18–192.
PASINO, E., BUFFELLI, M., ARANCIO, O., BUSETTO, G., SALVIATI, A. & CANGIANO, A. (1996) Effects of long-term conduction block onmembraneproperties of reinnervated and normally innervated rat skeletal muscle. Journal of Physiology 497(Pt 2), 45–472.
POCKETT, S. & SLACK, J. R. (1982) Source of the stimulus for nerve terminal sprouting in partially denervatedmuscle. Neuroscience 7, 317–3176.
RAFUSE, V. F. & GORDON, T. (1996a) Self-reinnervated cat medial gastrocnemius muscles. I. Comparisons of the capacity of regenerating nerves to form enlarged motor units after extensive peripheral nerve injuries. The Journal of Neurophysiology 75, 26–281.
RAFUSE, V. F. & GORDON, T. (1996b) Self-reinnervated cat medial gastrocnemius muscles. II. Analysis of the mechanisms and significance of fiber type grouping in reinnervated muscles. The Journal of Neurophysiology 75, 28–297.
RAFUSE, V. F., GORDON, T. & OROZCO, R. (1992) Proportional Enlargement of Motor Units After Partial Denervation of Cat Triceps Surae Muscles. The Journal of Neurophysiology 68, 126–1275.
REHDER, V. & KATER, S. B. (1992) Regulation of neuronal growth cone filopodia by intracellular calcium. The Journal of Neuroscience 12, 317–3186.
REYNOLDS, M. L. & WOOLF, C. J. (1992) Terminal Schwann cells elaborate extensive processes following denervation of the motor endplate. The Journal of Neurocytology 21, 5–66.
RIBCHESTER, R. R. (1988) Activity-dependent and independent synaptic interactions during reinnervation of partially denervated rat muscle. The Journal of Physiology 401, 5–75.
ROCHON, D., ROUSSE, I. & ROBITAILLE, R. (2001) Synaptic-glia interactions at the mammalian neuromuscular junction. The Journal of Neuroscience 21, 381–3829.
RODNIGHT, R., GONCALVES, C. A., WOFCHUK, S. T. & LEAL, R. (1997) Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions: Possible key factor in astrocytic plasticity. The Journal of Medicine and Biological Research 30, 32–338.
SEBURN, K. L. & GARDINER, P. F. (1996) Properties of sprouted rat motor units: Effects of period of enlargement and activity level. Muscle & Nerve 19, 110–1109.
SLACK, J. R. & POCKETT, S. (1981) Terminal sprouting of motoneurones is a local response to a local stimulus. Brain Research 217, 36–374.
SON, Y. J. & THOMPSON, W. J. (1995a) Schwann cell processes guide regeneration of peripheral axons. Neuron 14, 12–132.
SON, Y. J. & THOMPSON, W. J. (1995b) Nerve sprouting in muscle is induced and guided by processes extended by Schwann cells. Neuron 14, 13–141.
SON, Y. J., TRACHTENBERG, J. T. & THOMPSON, W. J. (1996) Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions. Trends in Neurosciences 19, 28–285.
SULAIMAN, O. A. R., BOYD, J. G. & GORDON, T. (2003) Regeneration in the peripheral system of mammals. Neuroglia (Accepted with revisions).
TAM, S. L., ARCHIBALD, V., TYREMAN, N. & GORDON, T. (2002a) Effect of exercise on stability of chronically enlarged motor units. Muscle & Nerve 25, 35–369.
TAM, S. L., ARCHIBALD, V., TYREMAN, N. & GORDON, T. (2002b) Tetrodotoxin prevents motor unit enlargement after partial denervation in rat hindlimb muscles. The Journal of Physiology 543, 65–663.
TAM, S. L., ARCHIBALD, V., TYREMAN, N., JASSAR, B. & GORDON, T. (2001) Increased neuromuscular activity reduces sprouting in partially denervated muscles. The Journal of Neuroscience 21, 65–667.
TAM, S. L. & GORDON, T. (2003) Neuromuscular activity impairs the function of terminal Schwann cells in muscle reinnervation by sprouting. The Journal of Neurobiology (Manuscript submitted).
THOMPSON, W. J. & JANSEN, J. K. (1977) The extent of sprouting of remaining motor units in partly denervated immature and adult rat soleusmuscle. Neuroscience 2, 52–535.
THOMPSON, W. J. & KOPP, D. M. (1996) Schwann cells accompany nerve sprouts induced inmuscle by insulin-like growth factors. Society for Neuroscience Abstract 22, 297.7.
TROJAN, D. A., GENDRON, D. & CASHMAN, N. R. (1991) Electrophysiology and electrodiagnosis of the postpolio motor unit. Orthopedics 14, 135–1361.
YANG, J. F., STEIN, R. B., JHAMANDAS, J. & GORDON, T. (1990) Motor unit numbers and contractile properties after spinal cordinjury. Annual Review ofNeurology 28, 49–502.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tam, S.L., Gordon, T. Mechanisms controlling axonal sprouting at the neuromuscular junction. J Neurocytol 32, 961–974 (2003). https://doi.org/10.1023/B:NEUR.0000020635.41233.0f
Issue Date:
DOI: https://doi.org/10.1023/B:NEUR.0000020635.41233.0f