Skip to main content
SpringerLink
Log in

Neuromuscular Synapse Elimination

Structural, Functional, and Mechanistic Aspects

  • Chapter
Neuronal Development

Part of the book series: Current Topics in Neurobiology ((CTNB))

Abstract

It is well known that synaptic connections are established with a high degree of specificity during the development of the nervous system. Nonetheless, the pattern of connections at early stages of neurogenesis differs from that in the adult in several important respects. Two major phases of reorganization are now recognized to be common to the maturation of many parts of the nervous system. In the first phase there is widespread neuronal death, which generally occurs around the time of synapse formation. Neuronal death appears to be primarily a mechanism for adjusting the number of cells in a given structure to the number of target cells available and secondarily a mechanism for eliminating cells which have aberrant connections1,2 (see Chapter 9). The second phase of reorganization involves extensive remodeling of synaptic connections without attendant cell death. In some parts of the nervous system the majority of synapses initially formed are subsequently eliminated.1–3 Although many unanswered questions pertain to the functional significance of synapse elimination, it is a basic phenomenon in neurogenesis and is deserving of careful scrutiny.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cowan, W. M., 1978, Aspects of neural development, Int. Rev. Physiol. 17: 149.

    Google Scholar 

  2. Jacobson, M., 1978, Developmental Neurobiology, 2nd ed., Plenum Press, New York.

    Google Scholar 

  3. Dennis, M. J., 1981, Development of the neuromuscular junction: Inductive interactions between cells, Ann. Rev. Neurosci. 4: 43.

    Google Scholar 

  4. Tello, J. F., 1917, Genesis de las terminaciones nerviosas motrices y sensitivas, Trab. Lab. Invest. Biol. Madrid 15: 101.

    Google Scholar 

  5. Cuajunco, F., 1942, Development of the human motor end-plate, Carnegie Inst. Contr. Embryol. 30: 129.

    Google Scholar 

  6. Redfern, P. A., 1970, Neuromuscular transmission in new-born rats, J. Physiol. 209: 701.

    Google Scholar 

  7. Brown, M. C., Jansen, J. K. S., and Van Essen, D., 1976, Polyneuronal innervation of skeletal muscle in new-born rats and its elimination during maturation, J. Physiol. 261: 387.

    Google Scholar 

  8. Bagust, J., Lewis, D. M., and Westerman, R. A., 1973, Polyneuronal innervation of kitten skeletal muscle, J. Physiol. 229: 241.

    Google Scholar 

  9. Bennett, M. R., and Pettigrew, A. G., 1974, The formation of synapses in striated muscle during development, J. Physiol. 241: 515.

    Google Scholar 

  10. Dennis, M. J., Ziskind-Conhaim, L., and Harris, A. J., 1981, Development of neuromuscular junctions in rat embryos, Dev. Biol. 81: 266.

    Google Scholar 

  11. Ontell, M., and Dunn, R. F., 1978, Neonatal muscle growth: A quantitative study, Am. J. Anat. 152: 539.

    Google Scholar 

  12. Betz, W. J., Caldwell, J. H., and Ribchester, R. R., 1979, The size of motor units during post-natal development of rat lumbrical muscle, J. Physiol. 297: 463.

    Google Scholar 

  13. Lubinska, L., and Zelenâ, J., 1966, Formation of new sites of acetylcholinesterase activity in denervated muscle of young rats, Nature (London) 210: 39.

    Google Scholar 

  14. Riley, D. A., 1976, Multiple axon branches innervating single endplates of kitten soleus myofibers, Brain Res. 110: 158.

    Google Scholar 

  15. Bixby, J. L., and Van Essen, D. C., 1979, Regional differences in the timing of synapse elimination in skeletal muscles of the neonatal rabbit, Brain Res. 169: 275.

    Google Scholar 

  16. Bennett, M. R., and Pettigrew, A. G., 1975, The formation of synapses in amphibian striated muscle during development, J. Physiol. 252: 203.

    Google Scholar 

  17. Rosenthal, J. L., and Taraskevitch, P. S., 1977, Reduction of multiaxonal innervation at the neuromuscular junction of the rat during development, J. Physiol. 270: 299.

    Google Scholar 

  18. Harris-Flanagan, A. E., 1969, Differentiation and degeneration in the motor horn of the foetal mouse, J. Morphol. 129: 281.

    Google Scholar 

  19. Chiakulas, J. J., and Pauly, J. E., 1965, A study of postnatal growth of skeletal muscle in the rat, Anat. Rec. 152: 55.

    Google Scholar 

  20. Rayne, J., and Crawford, G. N. C., 1975, Increase in fibre numbers of the rat pterygoid muscles during postnatal growth, J. Anat. 119: 347.

    Google Scholar 

  21. Rowe, R. W. D., and Goldspink, G., 1969, Muscle fibre growth in five different muscles in both sexes of mice. I. Normal mice, J. Anat. 104: 519.

    Google Scholar 

  22. Enesco, M., and Puddy, D., 1964, Increase in the number of nuclei and weight in skeletal muscle of rats of various ages, Am. J. Anat. 114: 235.

    Google Scholar 

  23. Thompson, W., and Jansen, J. K. S., 1977, The extent of sprouting of remaining motor units in partly denervated immature and adult rat soleus muscle, Neuroscience 2: 523.

    Google Scholar 

  24. Westerman, R. A., Lewis, D. M., Bagust, J., Edjtehadi, G. D., and Pallot, D., 1973, Communication between nerves and muscles: Postnatal development in kitten hind-limb fast and slow twitch muscle, in: Memory and Transfer of Information, ( H. P. Zippel, ed.), pp. 255–291, Plenum Press, New York.

    Google Scholar 

  25. Riley, D. A., 1977, Spontaneous elimination of nerve terminals from the endplates of developing skeletal myofibers, Brain Res. 134: 279.

    Google Scholar 

  26. O’Brien, R. A. D., Östberg, A. J. C., and Vrbovâ, G., 1978, Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle, J. Physiol. 282: 571.

    Google Scholar 

  27. Brown, M. C., Holland, R. L., and Hopkins, W. G., 1981, Excess neuronal inputs during development, in: Development in the Nervous System,(D. R. Garrod and J. D. Feldman, eds.), Cambridge University Press, Cambridge, in press.

    Google Scholar 

  28. Gordon, H., and Van Essen, D. C., 1981, Motor units diversify in size as synapse elimination proceeds in the neonatal rabbit soleus muscle, Soc. Neurosci. Abstr., 7: 179.

    Google Scholar 

  29. Hubel, D. H., and Wiesel, T. N., 1970, The period of susceptibility to the physiological effects of unilateral eye closure in kittens, J. Physiol. 206: 419.

    Google Scholar 

  30. LeVay, S., Wiesel, T. N., and Hubel, D. H., 1980, The development of ocular dominance columns in normal and visually deprived monkeys, J. Comp. Neurol. 191: 1.

    Google Scholar 

  31. Frank, E., Jansen, J. K. S., Lemo, T., and Westgaard, R. H., 1975, The interaction between foreign and original motor nerves innervating the soleus muscle of rats, J. Physiol. 247: 725.

    Google Scholar 

  32. Kuffler, D. P., Thompson, W., and Jansen, J. K. S., 1980, The fate of foreign endplates in cross-innervated rat soleus muscle. Proc. R. Soc. London Ser. B 208: 189.

    Google Scholar 

  33. Lemo, T., 1980, What controls the development of neuromuscular junctions? Trends Neurosci. 3: 126.

    Google Scholar 

  34. McArdle, J. J., 1975, Complex end-plate potentials at the regenerating neuromuscular junction of the rat, Exp. Neurol. 49: 629.

    Google Scholar 

  35. Brown, M. C., and Ironton, R., 1978, Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles, J. Physiol. 278: 325.

    Google Scholar 

  36. Bixby, J. L., and Van Essen, D. C., 1979, Competition between foreign and original nerves in adult mammalian skeletal muscle, Nature (London) 282: 726.

    Google Scholar 

  37. Korneliussen, H., and Jansen, J. K. S., 1976, Morphological aspects of the elimination of polyneuronal innervation of skeletal muscle fibres in newborn rats, J. Neurocytol. 5: 591.

    Google Scholar 

  38. Bixby, J. L., 1981, Ultrastructural observations on synapse elimination in neonatal rabbit skeletal muscle, J. Neurocytol. 10: 81.

    Google Scholar 

  39. Riley, D. A., 1981, Ultrastructural evidence of axon retraction during the spontaneous elimination of polyneuronal innervation of the rat soleus muscle, J. Neurocytol. 10: 425.

    Google Scholar 

  40. Guth, L., and Zalewski, A. A., 1963, Disposition of cholinesterase following implantation of nerve into innervated and denervated muscle, Exp. Neurol. 7: 316.

    Google Scholar 

  41. Guth, L., Zalewski, A. A., and Brown, W. C., 1966, Quantitative changes in cholinesterase activity of denervated sole plates following implantation of nerve into muscle, Exp. Neurol. 16: 136.

    Google Scholar 

  42. Gutmann, E., and Hanzhkovâ, V., 1967, Effects of accessory nerve supply to muscle achieved by implantation into muscle during regeneration of its nerve, Physiol. Bohemoslov. 16: 244.

    Google Scholar 

  43. Frank, E., Gautvik, K., and Sommerschild, H., 1975, Cholinergie receptors at denervated mammalian motor end-plates, Acta Physiol. Scand. 95: 66.

    Google Scholar 

  44. Marshall, L. M., Sanes, J. R., and McMahan, U. J., 1977, Reinnervation of original synaptic sites on muscle fiber basement membrane after disruption of the muscle cells, Proc. Natl. Acad. Sci. U.S.A. 74: 3073.

    Google Scholar 

  45. Sanes, J. R., Marshall, L. M., and McMahan, U. J., 1978, Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites, J. Cell Biol. 78: 176.

    Google Scholar 

  46. Burden, S. J., Sargent, P. B., and McMahan, U. J., 1979, Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve, J. Cell Biol. 82: 412.

    Google Scholar 

  47. Young, J. Z., 1952, Growth and plasticity in the nervous system, Proc. R. Soc. London Ser. B 139: 18.

    Google Scholar 

  48. Barker, D., and Ip, M. C., 1966, Sprouting and degeneration of mammalian motor axons in normal and de-afferentated skeletal muscle, Proc. R. Soc. London Ser. B 163: 538.

    Google Scholar 

  49. Tuffery, A. R., 1971, Growth and degeneration of motor end-plates in normal cat hind limb muscles, J. Anat. 110: 221.

    Google Scholar 

  50. Brown, M. C., and Ironton, R., 1977, Motor neurone sprouting induced by prolonged tetrodotoxin block of nerve action potentials, Nature (London) 265: 459.

    Google Scholar 

  51. Letinsky, M. S., Fischbeck, K. H., and McMahan, U. J., 1976, Precision of reinnervation of original postsynaptic sites in frog muscle after a nerve crush, J. Neurocytol. 5: 691.

    Google Scholar 

  52. Wernig, A., Pécot-Dechavassine, M., and Stöver, H., 1980, Sprouting and regression of the nerve at the frog neuromuscular junction in normal conditions and after prolonged paralysis with curare, J. Neurocytol. 9: 277.

    Google Scholar 

  53. Haimann, C., Mallart, A., Tomas i Ferré, J., and Zilber-Gachelin, N. F., 1981, Patterns of motor innervation in the pectoral muscle of adult Xenopus laevis: Evidence for possible synaptic remodeling, J. Physiol. 310: 241.

    Google Scholar 

  54. Speidel, C. C., 1942, Studies of living nerves. VII. Growth adjustments of cutaneous terminal arborizations, J. Corp. Neurol. 76: 57.

    Google Scholar 

  55. Betz, W. J., Caldwell, J. H., and Ribchester, R. R., 1980, The effects of partial denervation at birth on the development of muscle fibres and motor units in rat lumbrical muscle, J. Physiol. 303: 265.

    Google Scholar 

  56. Dennis, M. J., and Harris, A. J., 1980, Transient inability of neonatal rat motoneurons to reinnervate muscle, Dev. Biol. 74: 173.

    Google Scholar 

  57. Brown, M. C., Holland, R. L., and Hopkins, W. G., 1980, Some effects of botulinum toxin on the motor innervation of neonatal rat muscles, J. Physiol. 307: 17 p.

    Google Scholar 

  58. Bennett, M. R., and Pettigrew, A. G., 1974, The formation of synapses in reinnervated and cross-reinnervated striated muscle during development, J. Physiol. 241: 547.

    Google Scholar 

  59. Mark, R. F., 1980, Synaptic repression at neuromuscular junctions, Physiol. Rev. 60: 355.

    Google Scholar 

  60. Proctor, W., Frenk, S., Taylor, B., and Roper, S., 1979, “Hybrid” synapses formed by foreign innervation of parasympathetic neurons: A model for selectivity during competitive reinnervation, Proc. Natl. Acad. Sci. U.S.A. 76:4695.

    Google Scholar 

  61. Close, R., 1967, Properties of motor units in fast and slow skeletal muscles of the rat, J. Physiol. 193: 45.

    Google Scholar 

  62. Miyata, Y., and Yoshioka, K., 1980, Selective elimination of motor nerve terminals in the rat soleus muscle during development, J. Physiol. 309: 631.

    Google Scholar 

  63. Swett, J. E., Eldred, E., and Buchwald, J. S., 1970, Somatotopic cord-to-muscle relations in efferent innervation of cat gatrocnemius, Am. J. Physiol. 219: 762.

    Google Scholar 

  64. Harris, W. A., 1981, Neural activity and development, Ann. Rev. Physiol. 43: 689.

    Google Scholar 

  65. Cangiano, A., Lemo, T., Lutzemberger, L., and Sveen, O., 1980, Effects of chronic nerve conduction block on formation of neuromuscular junctions and junctional AChE in the rat, Acta Physiol. Scand. 109: 283.

    Google Scholar 

  66. Thompson, W., Kuffler, D. P., and Jansen, J. K. S., 1979, The effect of prolonged, reversible block of nerve impulses on the elimination of polyneuronal innervation of new-born rat skeletal muscle fibers, Neuroscience 4: 271.

    Google Scholar 

  67. Benoit, P., and Changeux, J.-P., 1975, Consequences of tenotomy on the evolution of multiinnervtion in developing rat soleus muscle, Brain Res. 99: 354.

    Google Scholar 

  68. Benoit, P., and Changeux, J.-P., 1978, Consequences of blocking the nerve with a local anaesthetic on the evolution of multiinnervation at the regenerating neuromuscular junction of the rat, Brain Res. 149: 89.

    Google Scholar 

  69. Purves, D., and Lichtman, J. W., 1980, Elimination of synapses in the developing nervous system, Science 210: 153.

    Google Scholar 

  70. Jansen, J. K. S., Thompson, W., and Kuffler, D. P., 1978, The formation and maintenance of synaptic connections as illustrated by studies of the neuromuscular junction, Progr. Brain Res. 48: 3.

    Google Scholar 

  71. O’Brien, R. A. D., Ostberg, A. J., and Vrbovâ, G., 1980, The effect of acetylcholine on the function and structure of the developing mammalian neuromuscular junction, Neuroscience 5: 1367.

    Google Scholar 

  72. Greene, L. A., and Shooter, E. M., 1980, The nerve growth factor: Biochemistry, synthesis, and mechanism of action., Ann. Rev. Neurosci. 3: 353.

    Google Scholar 

  73. Gundersen, R. W., and Barrett, J. N., 1979, Neuronal chemotaxis: Chick dorsal-root axons turn toward high concentrations of nerve growth factor, Science 206: 1079.

    Google Scholar 

  74. Campenot, R. B., 1977, Local control of neunte development by nerve growth factor, Proc. Natl. Acad. Sci. U.S.A. 74: 4516.

    Google Scholar 

  75. Bennett, M. R., and Nurcombe, V., 1979, The survival and development of cholinergic neurons in skeletal muscle conditioned media, Brain Res. 173: 543.

    Google Scholar 

  76. Obata, K., and Tanaka, H., 1980, Conditioned medium promotes neurite growth from both central and peripheral neurons, Neurosci. Lett. 16: 27.

    Google Scholar 

  77. Brown, M. C., Holland, R. L., and Hopkins, W. G., 1981, Motor nerve sprouting, Ann. Rev. Neurosci. 4: 17.

    Google Scholar 

  78. Betz, W. J., Caldwell, J. H., and Ribchester, R. R., 1980, Sprouting of active nerve terminals in partially inactive muscles of the rat, J. Physiol. 303: 281.

    Google Scholar 

  79. Brown, M. C., Holland, R. L., Hopkins, W. G., and Keynes, R. J., 1981, An assessment of the spread of the signal for terminal sprouting within and between muscles, Brain Res. 210: 145.

    Google Scholar 

  80. Bray, D., and Gilbert, D., 1981, Cytoskeletal elements in neurons, Ann. Rev. Neurosci. 4: 505.

    Google Scholar 

  81. Lento, T., and Slater, C. R., 1980, Control of junctional acetylcholinesterase by neural and muscular influences in the rat, J. Physiol. 303: 191.

    Google Scholar 

  82. Bate, C. M., 1976, Pioneer neurons in an insect embryo, Nature (London) 260: 54.

    Google Scholar 

  83. Grant, P., and Rubin, E., 1980, Ontogeny of the retina and optic nerve in Xenopus laevis. II. Ontogeny of the optic fiber pattern in the retina, J. Comp. Neurol. 189: 671.

    Google Scholar 

  84. Rutishauser, U., Gall, W. E., and Edelman, G. M., 1978, Adhesion among neural cells of the chick embryo. IV. Role of the cell surface molecule CAM in the formation of neurite bundles in cultures of spinal ganglia, J. Cell Biol. 79: 382.

    Google Scholar 

  85. Stent, G. S., 1973, A physiological mechanism for Hebb’s postulate of learning, Proc. Natl. Acad. Sci. U.S.A. 70: 997.

    Google Scholar 

  86. Slack, J. R., 1978, Interaction between foreign and regenerating axons in axolotl muscle. Brain Res. 146: 172.

    Google Scholar 

  87. Meyer, R. L., 1979, “Extra” optic fibers exclude normal fibers from tectal regions in goldfish, J. Comp. Neurol. 183:883.

    Google Scholar 

  88. Sanes, J. R., and Hall, Z. W., 1979, Antibodies that bind specifically to synaptic sites on muscle fiber basal lamina, J. Cell Biol. 83: 357.

    Google Scholar 

  89. Lichtman, J. W., 1977, The reorganization of synaptic connexions in the rat sub-mandibular ganglion during postnatal development, J. Physiol. 273: 155.

    Google Scholar 

  90. Lichtman, J. W., and Purves, D., 1980, The elimination of redundant preganglionic innervation to hamster sympathetic ganglion cells in early post-natal life, J. Physiol. 301: 213.

    Google Scholar 

  91. Purves, D., and Hume, R. I., 1981, The relation of postsynaptic geometry to the number of presynaptic axons that innervate autonomic ganglion cells, J. Neurosci. 1: 441.

    Google Scholar 

  92. Ronnevi, L. O., 1977, Spontaneous phagocytosis of boutons on spinal motoneurons during early postnatal development: An electron microscopical study in the cat, J. Neurocytol. 6: 487.

    Google Scholar 

  93. Knyihar, E., Csillik, B., and Rakic, P., 1978, Transient synapses in the embryonic primate spinal cord, Science 202: 1206.

    Google Scholar 

  94. Crepel, F., Marian, J. and Delhaye-Bouchad, N., 1976, Evidence for a multiple innervation of Purkinje cells by climbing fibers in the immature rat cerebellum, J. Neurobiol. 7: 567.

    Google Scholar 

  95. Boothe, R. G., Greenough, W. T., Lund, J. S., and Wrege, K., 1979, A quantitative investigation of spine and dendrite development of neurons in visual cortex (area 17) of Macaca nemestrina monkeys, J. Comp. Neurol. 186: 473.

    Google Scholar 

  96. Innocenti, G. M., 1981, Growth and reshaping of axons in the establishment of visual callosal connections, Science 212: 824.

    Google Scholar 

  97. Stephens, P. J., and Govind, C. K., 1981, Peripheral innervation fields of single lobster motoneurons defined by synapse elimination during development, Brain Res. 212: 476.

    Google Scholar 

  98. Hollyfield, J. G., 1971, Differential growth of the neural retina in Xenopus laevis larvae, Dev. Biol. 24: 264.

    Google Scholar 

  99. Meyer, R. L., 1978, Evidence from thymidine labeling for continuing growth of retina and tectum in juvenile goldfish, Exp. Neurol. 59: 99.

    Google Scholar 

  100. Gaze, R. M., Keating, M. J., Ostberg, A., and Chung, S.-H., 1979, The relationship between retinal and tectal growth in larval Xenopus: Implications for the development of the retino-tectal projection, J. Embryol. Exp. Morphol. 53: 103.

    Google Scholar 

  101. Sotelo, C., and Palay, S. L., 1971, Altered axons and axon terminals in the lateral vestibular nucleus of the rat, Lab. Invest. 25: 653.

    Google Scholar 

  102. Chan-Palay, V., 1973, Neuronal plasticity in the cerebellar cortex and lateral nucleus, Z. Anat. Entwicklungsgesch. 142: 23.

    Google Scholar 

  103. Rakic, P., 1976, Prenatal genesis of connections subserving ocular dominance in the rhesus monkey, Nature (London) 261: 467.

    Google Scholar 

  104. LeVay, S., Stryker, M. P., and Shatz, C. J., 1978, Ocular dominance columns and their development in layer IV of the cat’s visual cortex: A quantitative study, J. Comp. Neurol. 179: 223.

    Google Scholar 

  105. Stryker, M. P., 1981, Late segregation of geniculate afferents to the cat’s visual cortex after recovery from binocular impulse blockade, Soc. Neurosci. Abstr. 7: 842.

    Google Scholar 

  106. Swindale, N. V., 1981, Absence of ocular dominance patches in dark-reared cats, Nature (London) 290: 332.

    Google Scholar 

  107. Dennis, M. J., and Harris, A. J., 1979, Elimination of inappropriate nerve-muscle connections during development of rat embryos, Progr. Brain Res. 49: 359.

    Google Scholar 

  108. Landmesser, L. T., 1980, The generation of neuromuscular specificity, Ann. Rev. Neurosci. 3: 279.

    Google Scholar 

  109. Pettigrew, J. D., 1974, The effect of visual experience on the development of stimulus specificity by kitten cortical neurones, J. Physiol. 237: 49.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biology 216-76, California Institute of Technology, Pasadena, CA, 91125, USA

    David C. van Essen

Authors
  1. David C. van Essen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California, San Diego, La Jolla, California, USA

    Nicholas C. Spitzer

Rights and permissions

Reprints and permissions

Copyright information

© 1982 Plenum Press, New York

About this chapter

Cite this chapter

van Essen, D.C. (1982). Neuromuscular Synapse Elimination. In: Spitzer, N.C. (eds) Neuronal Development. Current Topics in Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1131-7_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-1131-7_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-1133-1

  • Online ISBN: 978-1-4684-1131-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation