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.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Cowan, W. M., 1978, Aspects of neural development, Int. Rev. Physiol. 17: 149.
Jacobson, M., 1978, Developmental Neurobiology, 2nd ed., Plenum Press, New York.
Dennis, M. J., 1981, Development of the neuromuscular junction: Inductive interactions between cells, Ann. Rev. Neurosci. 4: 43.
Tello, J. F., 1917, Genesis de las terminaciones nerviosas motrices y sensitivas, Trab. Lab. Invest. Biol. Madrid 15: 101.
Cuajunco, F., 1942, Development of the human motor end-plate, Carnegie Inst. Contr. Embryol. 30: 129.
Redfern, P. A., 1970, Neuromuscular transmission in new-born rats, J. Physiol. 209: 701.
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.
Bagust, J., Lewis, D. M., and Westerman, R. A., 1973, Polyneuronal innervation of kitten skeletal muscle, J. Physiol. 229: 241.
Bennett, M. R., and Pettigrew, A. G., 1974, The formation of synapses in striated muscle during development, J. Physiol. 241: 515.
Dennis, M. J., Ziskind-Conhaim, L., and Harris, A. J., 1981, Development of neuromuscular junctions in rat embryos, Dev. Biol. 81: 266.
Ontell, M., and Dunn, R. F., 1978, Neonatal muscle growth: A quantitative study, Am. J. Anat. 152: 539.
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.
Lubinska, L., and Zelenâ, J., 1966, Formation of new sites of acetylcholinesterase activity in denervated muscle of young rats, Nature (London) 210: 39.
Riley, D. A., 1976, Multiple axon branches innervating single endplates of kitten soleus myofibers, Brain Res. 110: 158.
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.
Bennett, M. R., and Pettigrew, A. G., 1975, The formation of synapses in amphibian striated muscle during development, J. Physiol. 252: 203.
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.
Harris-Flanagan, A. E., 1969, Differentiation and degeneration in the motor horn of the foetal mouse, J. Morphol. 129: 281.
Chiakulas, J. J., and Pauly, J. E., 1965, A study of postnatal growth of skeletal muscle in the rat, Anat. Rec. 152: 55.
Rayne, J., and Crawford, G. N. C., 1975, Increase in fibre numbers of the rat pterygoid muscles during postnatal growth, J. Anat. 119: 347.
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.
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.
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.
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.
Riley, D. A., 1977, Spontaneous elimination of nerve terminals from the endplates of developing skeletal myofibers, Brain Res. 134: 279.
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.
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.
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.
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.
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.
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.
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.
Lemo, T., 1980, What controls the development of neuromuscular junctions? Trends Neurosci. 3: 126.
McArdle, J. J., 1975, Complex end-plate potentials at the regenerating neuromuscular junction of the rat, Exp. Neurol. 49: 629.
Brown, M. C., and Ironton, R., 1978, Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles, J. Physiol. 278: 325.
Bixby, J. L., and Van Essen, D. C., 1979, Competition between foreign and original nerves in adult mammalian skeletal muscle, Nature (London) 282: 726.
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.
Bixby, J. L., 1981, Ultrastructural observations on synapse elimination in neonatal rabbit skeletal muscle, J. Neurocytol. 10: 81.
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.
Guth, L., and Zalewski, A. A., 1963, Disposition of cholinesterase following implantation of nerve into innervated and denervated muscle, Exp. Neurol. 7: 316.
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.
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.
Frank, E., Gautvik, K., and Sommerschild, H., 1975, Cholinergie receptors at denervated mammalian motor end-plates, Acta Physiol. Scand. 95: 66.
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.
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.
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.
Young, J. Z., 1952, Growth and plasticity in the nervous system, Proc. R. Soc. London Ser. B 139: 18.
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.
Tuffery, A. R., 1971, Growth and degeneration of motor end-plates in normal cat hind limb muscles, J. Anat. 110: 221.
Brown, M. C., and Ironton, R., 1977, Motor neurone sprouting induced by prolonged tetrodotoxin block of nerve action potentials, Nature (London) 265: 459.
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.
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.
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.
Speidel, C. C., 1942, Studies of living nerves. VII. Growth adjustments of cutaneous terminal arborizations, J. Corp. Neurol. 76: 57.
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.
Dennis, M. J., and Harris, A. J., 1980, Transient inability of neonatal rat motoneurons to reinnervate muscle, Dev. Biol. 74: 173.
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.
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.
Mark, R. F., 1980, Synaptic repression at neuromuscular junctions, Physiol. Rev. 60: 355.
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.
Close, R., 1967, Properties of motor units in fast and slow skeletal muscles of the rat, J. Physiol. 193: 45.
Miyata, Y., and Yoshioka, K., 1980, Selective elimination of motor nerve terminals in the rat soleus muscle during development, J. Physiol. 309: 631.
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.
Harris, W. A., 1981, Neural activity and development, Ann. Rev. Physiol. 43: 689.
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.
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.
Benoit, P., and Changeux, J.-P., 1975, Consequences of tenotomy on the evolution of multiinnervtion in developing rat soleus muscle, Brain Res. 99: 354.
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.
Purves, D., and Lichtman, J. W., 1980, Elimination of synapses in the developing nervous system, Science 210: 153.
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.
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.
Greene, L. A., and Shooter, E. M., 1980, The nerve growth factor: Biochemistry, synthesis, and mechanism of action., Ann. Rev. Neurosci. 3: 353.
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.
Campenot, R. B., 1977, Local control of neunte development by nerve growth factor, Proc. Natl. Acad. Sci. U.S.A. 74: 4516.
Bennett, M. R., and Nurcombe, V., 1979, The survival and development of cholinergic neurons in skeletal muscle conditioned media, Brain Res. 173: 543.
Obata, K., and Tanaka, H., 1980, Conditioned medium promotes neurite growth from both central and peripheral neurons, Neurosci. Lett. 16: 27.
Brown, M. C., Holland, R. L., and Hopkins, W. G., 1981, Motor nerve sprouting, Ann. Rev. Neurosci. 4: 17.
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.
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.
Bray, D., and Gilbert, D., 1981, Cytoskeletal elements in neurons, Ann. Rev. Neurosci. 4: 505.
Lento, T., and Slater, C. R., 1980, Control of junctional acetylcholinesterase by neural and muscular influences in the rat, J. Physiol. 303: 191.
Bate, C. M., 1976, Pioneer neurons in an insect embryo, Nature (London) 260: 54.
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.
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.
Stent, G. S., 1973, A physiological mechanism for Hebb’s postulate of learning, Proc. Natl. Acad. Sci. U.S.A. 70: 997.
Slack, J. R., 1978, Interaction between foreign and regenerating axons in axolotl muscle. Brain Res. 146: 172.
Meyer, R. L., 1979, “Extra” optic fibers exclude normal fibers from tectal regions in goldfish, J. Comp. Neurol. 183:883.
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.
Lichtman, J. W., 1977, The reorganization of synaptic connexions in the rat sub-mandibular ganglion during postnatal development, J. Physiol. 273: 155.
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.
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.
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.
Knyihar, E., Csillik, B., and Rakic, P., 1978, Transient synapses in the embryonic primate spinal cord, Science 202: 1206.
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.
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.
Innocenti, G. M., 1981, Growth and reshaping of axons in the establishment of visual callosal connections, Science 212: 824.
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.
Hollyfield, J. G., 1971, Differential growth of the neural retina in Xenopus laevis larvae, Dev. Biol. 24: 264.
Meyer, R. L., 1978, Evidence from thymidine labeling for continuing growth of retina and tectum in juvenile goldfish, Exp. Neurol. 59: 99.
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.
Sotelo, C., and Palay, S. L., 1971, Altered axons and axon terminals in the lateral vestibular nucleus of the rat, Lab. Invest. 25: 653.
Chan-Palay, V., 1973, Neuronal plasticity in the cerebellar cortex and lateral nucleus, Z. Anat. Entwicklungsgesch. 142: 23.
Rakic, P., 1976, Prenatal genesis of connections subserving ocular dominance in the rhesus monkey, Nature (London) 261: 467.
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.
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.
Swindale, N. V., 1981, Absence of ocular dominance patches in dark-reared cats, Nature (London) 290: 332.
Dennis, M. J., and Harris, A. J., 1979, Elimination of inappropriate nerve-muscle connections during development of rat embryos, Progr. Brain Res. 49: 359.
Landmesser, L. T., 1980, The generation of neuromuscular specificity, Ann. Rev. Neurosci. 3: 279.
Pettigrew, J. D., 1974, The effect of visual experience on the development of stimulus specificity by kitten cortical neurones, J. Physiol. 237: 49.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights 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