Comprehensive Physiology Wiley Online Library

Neuromuscular Adaptation

Full Article on Wiley Online Library


The sections in this article are:

1 Matching of Motoneurons and Muscle Fiber Properties During Normal Development
1.1 Muscle Development
1.2 Motoneuron Development
1.3 Synapse Elimination
1.4 Summary
2 Neural and Nonneural Sources of Control of Adult Skeletal Muscle Properties
2.1 Cross‐Reinnervation
2.2 Prolonged Electrical Silence
3 Morphological and Metabolic Properties of Motoneurons
3.1 Relationship of Soma Size and Metabolic Properties
3.2 Adaptability of Soma Size and Metabolic Properties
4 Gene Amplification Within a Motor Unit
5 Overall Summary
Figure 1. Figure 1.

The three major types of myoblasts—embryonic or primary myoblasts, fetal or secondary myoblasts, and adult myoblasts or satellite cells—are separated primarily by the developmental stage at which they migrate from the somite to the limb bud.

Figure 2. Figure 2.

A schematic of the emergence of myosin heavy chain types from primary and secondary myotubes at the fetal, neonatal, and postnatal stages of development.

Figure 3. Figure 3.

A schematic of some of the factors potentially involved in the neural control of expression of AChR via the neuromuscular junction. Note that AChR transcription is repressed in extrajunctional nuclei by activity, perhaps via protein kinase C and Myo‐D–like transcription factors. Activity may also affect the junctional nuclei via receptors involving agrin and FGF, which may cause AChR clustering by stimulating tyrosine phosphorylation and AChR‐43KDa interactions; ARIA and CGRP could also affect junctional nuclei via separate receptors.

Figure 1.

The three major types of myoblasts—embryonic or primary myoblasts, fetal or secondary myoblasts, and adult myoblasts or satellite cells—are separated primarily by the developmental stage at which they migrate from the somite to the limb bud.

Figure 2.

A schematic of the emergence of myosin heavy chain types from primary and secondary myotubes at the fetal, neonatal, and postnatal stages of development.

Figure 3.

A schematic of some of the factors potentially involved in the neural control of expression of AChR via the neuromuscular junction. Note that AChR transcription is repressed in extrajunctional nuclei by activity, perhaps via protein kinase C and Myo‐D–like transcription factors. Activity may also affect the junctional nuclei via receptors involving agrin and FGF, which may cause AChR clustering by stimulating tyrosine phosphorylation and AChR‐43KDa interactions; ARIA and CGRP could also affect junctional nuclei via separate receptors.

 1. Amphlett, G. W., S. V. Perry, H. Syska, M. D. Brown, and G. Vrbova. Cross innervation and the regulatory protein system of rabbit soleus muscle. Nature 257: 602–604, 1975.
 2. Bagust, J., D. M. Lewis, and R. A. Westerman. Motor units in cross‐reinnervated fast and slow twitch muscle of the cat. J Physiol. (Land.) 313: 223–235, 1981.
 3. Baldwin, K. M., R. R. Roy, V. R. Edgerton, and R. E. Herrick. Interaction of nerve activity and skeletal muscle mechanical activity in regulating isomyosin expression. In: Advances in Myochemistry, edited by G. Benzi. London: John Libbey Eurotext, Ltd., 1989, p. 83–92.
 4. Balice‐Gordon, R. J., C. K. Chua, C. C. Nelson, and J. W. Lichtman. Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions. Neuron 11: 801–815, 1993.
 5. Balice‐Gordon, R. J., and J. W. Lichtman. In vivo visualization of the growth of pre‐ and postsynaptic elements of neuromuscular junctions in the mouse. J. Neurosci. 10: 894–908, 1990.
 6. Balice‐Gordon, R. J., and W. J. Thompson. The organization and development of compartmentalized innervation in rat extensor digitorum longus muscle. J. Physiol. (Lond.) 398: 211–231, 1988.
 7. Barany, M. ATPase activity of myosin correlated with speed of muscle shortening. J. Gen. Physiol. 50 (Suppl): 197–218, 1967.
 8. Barany, M., and R. I. Close. The transformation of myosin in cross‐innervated rat muscles. J. Physiol. (Lond.) 213: 455–474, 1971.
 9. Barde, Y. A. Trophic factors and neuronal survival. Neuron 2: 1525–1534, 1989.
 10. Barrett, J. N., and W. E. Crill. Specific membrane resistivity of dye‐injected cat motoneurons. Brain Res. 28: 556–561, 1971.
 11. Barrett, J. N., and W. E. Crill. Specific membrane properties of cat motoneurones. J. Physiol. (Lond.) 239: 301–324, 1974.
 12. Bennett, M. R., and N. A. Lavidis. Development of the topographical projection of motor neurons to a rat muscle accompanies loss of polyneuronal innervation. J. Neurosci. 4: 2204–2212, 1984.
 13. Betz, W. J., J. H. Caldwell, and R. R. Ribchester. The effects of partial denervation at birth on the development of muscle fibres and motor units in rat lumbrical muscle. J. Physiol. (Lond.) 303: 265–279, 1980.
 14. Betz, H., and J. P. Changeux. Regulation of muscle acetylcholine receptor synthesis in vitro by cyclic nucleotide derivatives. Nature 278: 749–752, 1979.
 15. Betz, W. J., R. R. Ribchester, and R. M. Ridge. Competitive mechanisms underlying synapse elimination in the lumbrical muscle of the rat. J. Neurobiol. 21: 1–17, 1990.
 16. Bixby, J. L. Ultrastructural observations on synapse elimination in neonatal rabbit skeletal muscle. J. Neurocytol. 10: 81–100, 1981.
 17. Bradshaw, R. A., T. L. Blundell, R. Lapatto, N. Q. McDonald, and J. Murray‐Rust. Nerve growth factor revisited. Trends Biochem. Sci. 18: 48–52, 1993.
 18. Bray, J. J., J. I. Hubbard, and R. G. Mills. The trophic influence of tetrodotoxin‐inactive nerves on normal and reinnervated rat skeletal muscles. J. Physiol. (Lond.) 297: 479–491, 1979.
 19. Brenner, H. R., V. Witzemann, and B. Sakmann. Imprinting of acetylcholine receptor messenger RNA accumulation in mammalian neuromuscular synapses. Nature 344: 544–547, 1990.
 20. Brooke, M. H., and K. K. Kaiser. Three “myosin adenosine triphosphatase” systems: the nature of their pH lability and sulfhydryl dependence. J. Histochem. Cytochem. 18: 670–672, 1970.
 21. Brown, M. C., and C. M. Booth. Postnatal development of the adult pattern of motor axon distribution in rat muscle. Nature 304: 741–742, 1983.
 22. Brown, M. C., W. G. Hopkins, and R. J. Keynes. Short‐ and long‐term effects of paralysis on the motor innervation of two different neonatal mouse muscles. J. Physiol. (Lond.) 329: 439–450, 1982.
 23. Brown, M. C., J. K. Jansen, and D. Van Essen. Polyneuronal innervation of skeletal muscle in new‐born rats and its elimination during maturation. J. Physiol. (Lond.) 261: 387–422, 1976.
 24. Buller, A. J., J. C. Eccles, and R. M. Eccles. Interactions between motoneurones and muscles in respect of the characteristic speeds of their responses. J. Physiol. (Lond.) 150: 417–430, 1960.
 25. Burke, R. E. Motor units: anatomy, physiology and functional organization. In: Handbook of Physiology, The Nervous System, Motor Control, edited by V. B. Brooks. Bethesda, MD: Am. Physiol. Soc., 1981, p. 345–422.
 26. Burke, R. E., R. P. Dum, J. W. Fleshman, L. L. Glenn, A. Lev‐Tov, M. J. O'Donovan, and M. J. Pinter. A HRP study of the relation between cell size and motor unit type in cat ankle extensor motoneurons. J. Comp. Neurol. 209: 17–28, 1982.
 27. Burke, R. E. and V. R. Edgerton. Motor unit properties and selective involvement in movement. Exerc. Sport Sci. Rev. 3: 31–81, 1975.
 28. Burke, R. E., P. L. Strick, K. Kanda, C. C. Kim, and B. Walmsley. Anatomy of medial gastrocnemius and soleus motor nuclei in cat spinal cord. J. Neurophysiol. 40: 667–680, 1977.
 29. Butler, J., E. Cosmos, and J. Brierley. Differentiation of muscle fiber types in aneurogenic brachial muscles of the chick embryo. J. Exp. Zool. 224: 65–80, 1982.
 30. Caldwell, J. H., and R. M. Ridge. The effects of deafferentation and spinal cord transection on synapse elimination in developing rat muscles. J. Physiol. (Lond.) 339: 145–159, 1983.
 31. Callaway, E. M., J. M. Soha, and D. C. Van Essen. Competition favouring inactive over active motor neurons during synapse elimination. Nature 328: 422–426, 1987.
 32. Callaway, E. M., J. M. Soha, and D. C. Van Essen. Differential loss of neuromuscular connections according to activity level and spinal position of neonatal rabbit soleus motor neurons. J. Neurosurg. Sci. 9: 1806–1824, 1989.
 33. Campa, J. F., and W. K. Engel. Histochemistry of motor neurons and interneurons in the cat lumbar spinal cord. Neurology 20: 559–568, 1970.
 34. Chalmers, G. R., and V. R. Edgerton. Single motoneuron succinate dehydrogenase activity. J. Histochem. Cytochem, 37: 1107–1114, 1989.
 35. Chalmers, G. R., R. R. Roy, and V. R. Edgerton. Motoneuron and muscle fiber succinate dehydrogenase activity in control and overloaded plantaris. J. Appl. Physiol. 71: 1589–1592, 1991.
 36. Chalmers, G. R., R. R. Roy, and V. R. Edgerton. Adaptability of the oxidative capacity of motoneurons. Brain Res. 570: 1–10, 1992.
 37. Changeux, J. P. Compartmentalized transcription of acetylcholine receptor genes during motor endplate epigenesis. New Biol. 3: 413–429, 1991.
 38. Chevallier, A., and M. Kieny. On the role of the connective tissue in the patterning of the chick limb musculature. Roux Arch. Dev. Biol. 191: 227–280, 1982.
 39. Chevallier, A., M. Kieny, and A. Mauger. Limb‐somite relationship: origin of the limb musculature. J. Embryol. Exp. Morphol. 41: 245–258, 1977.
 40. Clarke, P. G. Developmental cell death: morphological diversity and multiple mechanisms. Anat. Embryol. 181: 195–213, 1990.
 41. Condon, K., L. Silberstein, H. M. Blau, and W. J. Thompson. Development of muscle fiber types in the prenatal rat hindlimb. Dev. Biol. 138: 256–274, 1990.
 42. Condon, K., L. Silberstein, H. M. Blau, and W. J. Thompson. Differentiation of fiber types in aneural musculature of the prenatal rat hindlimb. Dev. Biol. 138: 275–295, 1990.
 43. Cope, T. C., and B. D. Clark. Motor‐unit recruitment in self‐reinnervated muscle. J. Neurophysiol. 70: 1787–1796, 1993.
 44. Cossu, G., M. Pacifici, S. Adamo, M. Bouche, and M. Molinaro. TPA‐induced inhibition of the expression of differentiative traits in cultured myotubes: dependence on protein synthesis. Differentiation 21: 62–65, 1982.
 45. Creed, R. S., D. Denny‐Brown, J. C. Eccles, E. G. T. Liddell, and C. S. Sherrington. In: Reflex Activity of the Spinal Cord. London: Oxford University Press, 1932.
 46. Crow, M. T., and F. E. Stockdale. Myosin expression and specialization among the earliest muscle fibers of the developing avian limb. Dev. Biol. 113: 238–254, 1986.
 47. Cullheim, S. Relations between cell body size, axon diameter and axon conduction velocity of cat sciatic alpha‐motoneurons stained with horseradish peroxidase. Neurosci. Lett. 8: 17–20, 1978.
 48. Cunningham, T. J. Naturally occurring neuron death and its regulation by developing neural pathways. Int. Rev. Cytol. 74: 163–186, 1982.
 49. Dahm, L. M., and L. T. Landmesser. The regulation of intramuscular nerve branching during normal development and following activity blockade. Dev. Biol. 130: 621–644, 1988.
 50. Dahm, L. M., and L. T. Landmesser. The regulation of synaptogenesis during normal development and following activity blockade. J. Neurosci. 11: 238–255, 1991.
 51. Davies, J. A., and G. M. Cook. Growth cone inhibition — in important mechanism in neural development? Bioessays 13: 11–15, 1991.
 52. Davies, J. A., G. M. Cook, C. D. Stern, and R. J. Keynes. Isolation from chick somites of a glycoprotein fraction that causes collapse of dorsal root ganglion growth cones. Neuron 4: 11–20, 1990.
 53. Davis, S., T. H. Aldrich, D. M. Valenzuela, V. V. Wong, M. E. Furth, S. P. Squinto, and G. D. Yancopoulos. The receptor for ciliary neurotrophic factor. Science 253: 59–63, 1991.
 54. De La Porte, S., F. M. Vallette, J. Grassi, M. Vigny, and J. Koenig. Presynaptic or postsynaptic origin of acetylcholinesterase at neuromuscular junctions? An immunological study in heterologous nerve‐muscle cultures. Dev. Biol. 116: 69–77, 1986.
 55. DeNardi, C., S. Ausoni, P. Moretti, L. Gorza, M. Velleca, M. Buckingham, and S. Schiaffino. Type 2X‐myosin heavy chain is coded by a muscle fiber type‐specific and developmentally regulated gene. J. Cell Biol. 123: 823–835, 1993.
 56. Dennis, M. J., L. Ziskind‐Conhaim, and A. J. Harris. Development of neuromuscular junctions in rat embryos. Dev. Biol. 81: 266–279, 1981.
 57. Denny‐Brown, D. On the nature of postural reflexes. Proc. R. Soc. Lond. Ser. B 104: 252–300, 1929.
 58. Devanandan, M. S., R. M. Eccles, and R. A. Westerman. Single motor units of mammalian muscles. J. Physiol. (Lond.) 178: 359–367, 1965.
 59. Dhoot, G. K., S. V. Perry, and G. Vrbova. Changes in the distribution of the components of the troponin complex in muscle fibers after cross‐innervation. Exp. Neurol. 72: 513–530, 1981.
 60. Dive, C., C. D. Gregory, D. J. Phipps, D. L. Evans, A. E. Milner, and A. H. Wyllie. Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry. Biochim. Biopbys. Acta 1133: 275–285, 1992.
 61. Dodd, J., and T. M. Jessell. Axon guidance and the patterning of neuronal projections in vertebrates. Science 242: 692–699, 1988.
 62. Donahue, S. P., and A. W. English. Selective elimination of cross‐compartmental innervation in rat lateral gastrocnemius muscle. J. Neurosci. 9: 1621–1627, 1989.
 63. Donahue, S. P., A. W. English, R. L. Roden, and G. A. Schwartz. Tenotomy delays both synapse elimination and myogenesis in rat lateral gastrocnemius. Neuroscience 42: 275–282, 1991.
 64. Donselaar, Y., D. Kernell, and O. Eerbeek. Soma size and oxidative enzyme activity in normal and chronically stimulated motoneurones of the cat's spinal cord. Brain Res. 385: 22–29, 1986.
 65. Dum, R. P., M. J. O'Donovan, J. Toop, and R. E. Burke. Cross‐reinnervated motor units in cat muscle. I. Flexor digitorum longus muscle units reinnervated by soleus motoneurons. J. Neurophysiol. 54: 818–836, 1985.
 66. Dum, R. P., M. J. O'Donovan, J. Toop, P. Tsairis, M. J. Pinter, and R. E. Burke. Cross‐reinnervated motor units in cat muscle. II. Soleus muscle reinnervated by flexor digi‐torum longus motoneurons. J. Neurophysiol. 54: 837–851, 1985.
 67. Dusterhoft, S., and D. Pette. Satellite cells from slow rat muscle express low myosin under appropriate culture conditions. Differentiation 53: 25–33, 1993.
 68. Eccles, J. C., R. M. Eccles, and A. Lundberg. The action potentials of the alpha motoneurones supplying fast and slow muscles. J. Physiol. (Lond.) 142: 275–291, 1958.
 69. Edgerton, V. R., and R. R. Roy. Neuromuscular adaptations to actual and simulated spaceflight. In: Handbook of Physiology, Environmental Physiology, edited by M. J. Fregly and C. M. Blatteis. New York: Oxford University Press, 1995, p. 721–764.
 70. Edgerton, V. R., G. Goslow, Jr., S. A. Rasmussen, and S. A. Spector. Is resistance of a muscle to fatigue controlled by its motoneurones? Nature 285: 589–590, 1980.
 71. Edgerton, V. R., R. R. Roy, and G. R. Chalmers. Does the size principle give insight into the energy requirements of motoneurons? In: The Segmental Motor System, edited by M. D. Binder and L. M. Mendell. New York: Oxford University Press, 1989, p. 150–164.
 72. Eftimie, R., H. R. Brenner, and A. Buonanno. Myogenin and MyoD join a family of skeletal muscle genes regulated by electrical activity. Proc. Natl. Acad. Sci. U. S. A. 88: 1349–1353, 1991.
 73. Eldred, E., L. Smith, and V. R. Edgerton. Comparison of contraction times of a muscle and its motor units. Neurosci. Lett. 146: 199–202, 1992.
 74. Eldridge, L. Lumbrosacral spinal isolation in cat surgical preparation and health maintenance. Exp. Neurol. 83: 318–327, 1984.
 75. Eldridge, L., G. K. Dhoot, and W. F. Mommaerts. Neural influences on the distribution of troponin I isotypes in the cat. Exp. Neurol. 83: 328–346, 1984.
 76. Eldridge, L., M. Liebhold, and J. H. Steinbach. Alterations in cat skeletal neuromuscular junctions following prolonged inactivity. J. Physiol. (Lond.) 313: 529–545, 1981.
 77. Eldridge, L., and W. Mommaerts. Ability to electrically silent nerves to specify fast and slow muscle characteristics. In: Plasticity of Muscle, edited by D. Pette. Berlin: Walter de Gruyter, 1980, p. 325–337.
 78. English, A. W., and W. D. Letbetter. Anatomy and innervation patterns of cat lateral gastrocnemius and plantaris muscles. Am. J. Anat. 164: 67–77, 1982.
 79. Falls, D. L., D. A. Harris, F. A. Johnson, M. M. Morgan, G. Corfas, and G. D. Fischbach. Mr 42,000 ARIA: a protein that may regulate the accumulation of acetylcholine receptors at developing chick neuromuscular junctions. Cold Spring Harb. Symp. Quant. Biol. 55: 397–406, 1990.
 80. Fambrough, D. M. Control of acetylcholine receptors in skeletal muscle. Physiol. Rev. 59: 165–227, 1979.
 81. Feldman, J. L., and F. E. Stockdale. Skeletal muscle satellite cell diversity: satellite cells from fibres of different types in cell culture. Dev. Biol. 143: 320–334, 1990.
 82. Feldman, J. L., and F. E. Stockdale. Temporal appearance of satellite cells during myogenesis. Dev. Biol. 153: 217–226, 1992.
 83. Fischbach, G. D., and S. A. Cohen. The distribution of acetylcholine sensitivity over uninnervated and innervated muscle fibers grown in cell culture. Dev. Biol. 31: 147–162, 1973.
 84. Fladby, T. Postnatal loss of synaptic terminals in the normal mouse soleus muscle. Acta Physiol. Scand. 129: 229–238, 1987.
 85. Fladby, T., and J. K. Jansen. Postnatal loss of synaptic terminals in the partially denervated mouse soleus muscle. Acta Physiol. Scand. 129: 239–246, 1987.
 86. Fladby, T., and J. K. Jansen. Selective innervation of neonatal fast and slow muscle fibres before net loss of synaptic terminals in the mouse soleus muscle. Acta Physiol. Scand. 134: 561–562, 1988.
 87. Florini, J. R., D. Z. Ewton, and K. A. Magri. Hormones, growth factors, and myogenic differentiation. Annu. Rev. Physiol. 53: 201–216, 1991.
 88. Foehring, R. C., and J. B. Munson. Motoneuron and muscle‐unit properties after long‐term direct innervation of soleus muscle by medial gastrocnemius nerve in cat. J. Neurophysiol. 64: 847–861, 1990.
 89. Foehring, R. C., G. W. Sypert, and J. B. Munson. Motor‐unit properties following cross‐reinnervation of cat lateral gastrocnemius and soleus muscles with medial gastrocnemius nerve. I. Influence of motoneurons on muscle. J. Neurophysiol. 57: 1210–1226, 1987.
 90. Fredette, B. J., and L. T. Landmesser. A reevaluation of the role of innervation in primary and secondary myogenesis in developing chick muscle. Dev. Biol. 143: 19–35, 1991.
 91. Fuentes, M. E., and P. Taylor. Control of acetylcholinesterase gene expression during myogenesis. Neuron 10: 679–687, 1993.
 92. Fulton, B. P., and K. Walton. Electrophysiological properties of neonatal rat motoneurones studied in vitro. J. Physiol. (Lond.) 370: 651–678, 1986.
 93. Gardiner, P. F., M. Favron, and P. Corriveau. Histochemical and contractile responses of rat medial gastrocnemius to 2 weeks of complete disuse. Can. J. Physiol. Pharmacol. 70: 1075–1081, 1992.
 94. Gauthier, G. R, R. E. Burke, S. Lowey, and A. W. Hobbs. Myosin isozymes in normal and cross‐reinnervated cat skeletal muscle fibers. J. Cell Biol. 97: 756–771, 1983.
 95. Gibson, S. J., J. M. Polak, S. R. Bloom, I. M. Sabate, P. M. Mulderry, M. A. Ghatei, G. P. McGregor, J. F. Morrison, J. S. Kelly, R. M. Evans, et al. Calcitonin gene‐related peptide immunoreactivity in the spinal cord of man and of eight other species. J. Neurosci. 4: 3101–3111, 1984.
 96. Gillespie, M. J., T. Gordon, and P. R. Murphy. Motor units and histochemistry in rat lateral gastrocnemius and soleus muscles: evidence for dissociation of physiological and histochemical properties after reinnervation. J. Neurophysiol. 57: 921–937, 1987.
 97. Goldman, D., H. R. Brenner, and S. Heinemann. Acetylcholine receptor alpha‐, beta‐, gamma‐, and delta‐subunit mRNA levels are regulated by muscle activity. Neuron 1: 329–333, 1988.
 98. Gordon, H., and D. C. Van Essen. The relation of neuromuscular synapse elimination to spinal position of rabbit and rat soleus motoneurones. J. Physiol. (Lond.) 339: 591–597, 1983.
 99. Gordon, H., and D. C. Van Essen. Specific innervation of muscle fiber types in a developmentally polyinnervated muscle. Dev. Biol. 111: 42–50, 1985.
 100. Graham, S. C., R. R. Roy, C. Navarro, B. Jiang, D. Pierotti, S. Bodine‐Fowler, and V. R. Edgerton. Enzyme and size profiles in chronically inactive cat soleus muscle fibers. Muscle Nerve 15: 27–36, 1992.
 101. Guth, L., and F. J. Samaha. Procedure for the histochemical demonstration of actomyosin ATPase. Exp. Neurol. 28: 365–367, 1970.
 102. Hall, Z. W. Multiple forms of acetylcholinesterase and their distribution in endplate and non‐endplate regions of rat diaphragm muscle. J. Neurobiol. 4: 343–361, 1973.
 103. Hall, Z. W., and J. R. Sanes. Synaptic structure and development: the neuromuscular junction. Cell 10: 99–121, 1993.
 104. Hamburger, V. Cell death in the development of the lateral motor column of the chick embryo. J. Comp. Neurol. 160: 535–546, 1975.
 105. Hamburger, V, and R. Levi‐Montalcini. Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J. Exp. Zool. 111: 457–502, 1949.
 106. Harris, A. J. Embryonic growth and innervation of rat skeletal muscles. I. Neural regulation of muscle fibre numbers. Philos. Trans. R. Soc. Lond. [Biol.] 293: 257–277, 1981.
 107. Heeley, D. H., G. K. Dhoot, N. Frearson, S. V Perry, and G. Vrbova. The effect of cross‐innervation on the tropomyosin composition of rabbit skeletal muscle. EEBS Lett. 152: 282–286, 1983.
 108. Heffner, C. D., A. G. Lumsden, and D. D. O'Leary. Target control of collateral extension and directional axon growth in the mammalian brain. Science 247: 217–220, 1990.
 109. Helgren, M. E., S. P. Squinto, H. L. Davis, D. J. Parry, T. G. Boulton, C. S. Heck, Y. Zhu, G. D. Yancopoulos, R. M. Lindsay, and P. S. DiStefano. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell 76: 493–504, 1994.
 110. Henneman, E., and L. M. Mendell. Functional organization of motoneuron pool and its input. In: Handbook of Physiology, The Nervous System, Motor Control, edited by V. B. Brooks. Bethesda, MD: Am. Physiol. Soc., 1981, p. 423–507.
 111. Henneman, E., and C. B. Olson. Relations between structure and function in the design of skeletal muscles. J. Neurophysiol. 28: 581–598, 1965.
 112. Henneman, E., G. Somjen, and D. O. Carpenter. Functional significance of cell size in spinal motoneurons. J. Neurophysiol. 28: 560–580, 1965.
 113. Hennig, R. and T. Lomo. Firing patterns of motor units in normal rats. Nature 314: 164–166, 1985.
 114. Hofer, M. M., and Y. A. Barde. Brain‐derived neurotrophic factor prevents neuronal death in vivo. Nature 331: 261–262, 1988.
 115. Hoffman, S. J., R. R. Roy, C. E. Blanco, and V. R. Edgerton. Enzyme profiles of single muscle fibers never exposed to normal neuromuscular activity. J. Appl. Physiol. 69: 1150–1158, 1990.
 116. Hoh, J. F. Neural regulation of mammalian fast and slow muscle myosins: an electrophoretic analysis. Biochemistry 14: 742–747, 1975.
 117. Hoh, J. F., S. Hughes, and J. Hoy. Myogenic and neurogenic regulation of myosin gene expression in cat jaw‐closing muscles regenerating in fast and slow limb muscle beds. J. Muscle Res. Cell Motil. 9: 59–72, 1988.
 118. Hollyday, M., and V. Hamburger. Reduction of the naturally occurring motor neuron loss by enlargement of the periphery. J. Comp. Neurol. 170: 311–320, 1976.
 119. Houenou, L. J., J. L. McManaman, D. Prevette, and R. W. Oppenheim. Regulation of putative muscle‐derived neurotrophic factors by muscle activity and innervation: in vivo and in vitro studies. J. Neurosci. 11: 2829–2837, 1991.
 120. Hughes, S. M., and H. M. Blau. Muscle fiber pattern is independent of cell lineage in postnatal rodent development. Cell 68: 659–671, 1992.
 121. Huizar, P., M. Kuno, and Y. Miyata. Differentiation of motoneurones and skeletal muscles in kittens. J. Physiol. (Lond.) 252: 465–479, 1975.
 122. Ishihara, A., H. Araki, and Y. Nishihira. Menadione‐linked alpha‐glycerophosphate dehydrogenase activity of motoneurons in rat soleus and extensor digitorum longus neuron pools. Neurochem. Res. 14: 455–458, 1989.
 123. Ishihara, A., H. Naitoh, H. Araki, and Y. Nishihira. Soma size and oxidative enzyme activity of motoneurones supplying the fast twitch and slow twitch muscles in the rat. Brain Res. 446: 195–198, 1988.
 124. Ishihara, A., R. R. Roy, and V. R. Edgerton. Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior. Neuroscience 68: 813–822, 1995.
 125. Ishihara, A., S. Taguchi, H. Araki, and Y. Nishihira. Oxidative and glycolytic metabolism of the tibialis anterior motoneurons in the rat. Acta Physiol. Scand. 141: 129–130, 1991.
 126. Ishihara, A., S. Taguchi, H. Araki, and Y. Nishihira. Retrograde neuronal labeling of motoneurons in the rat by fluorescent tracers, and quantitative analysis of oxidative enzyme activity in labeled neurons. Neurosci. Lett. 124: 141–143, 1991.
 127. Ishihara, A., S. Taguchi, M. Itoh, and K. Itoh. Oxidative metabolism of the rat soleus neuron pool following hypobaric hypoxia. Brain Res. Bull. 24: 143–146, 1990.
 128. Jansen, J. K., and T. Fladby. The perinatal reorganization of the innervation of skeletal muscle in mammals. Prog. Neurobiol. 34: 39–90, 1990.
 129. Jasmin, B. J., R. K. Lee, and R. L. Rotundo. Compartmentalization of acetylcholinesterase mRNA and enzyme at the vertebrate neuromuscular junction. Neuron 11: 467–477, 1993.
 130. Jean, D. H., L. Guth, and R. W. Albers. Neural regulation of the structure of myosin. Exp. Neurol. 38: 458–471, 1973.
 131. Jiang, B. A., R. R. Roy, C. Navarro, Q. Nguyen, D. Pierotti, and V. R. Edgerton. Enzymatic responses of cat medial gastrocnemius fibers to chronic inactivity. J. Appl. Physiol. 70: 231–239, 1991.
 132. Jiang, B., R. R. Roy, I. V. Polyakov, I. B. Krasnov, and V. R. Edgerton. Ventral horn cell responses to spaceflight and hindlimb suspension. J. Appl. Physiol. 73 (Suppl.): 107S–111S, 1992.
 133. Jobsis, A. C., A. E. Meijer, and A. H. Vloedman. Alteration of the maximal activity of the gluconeogenetic enzyme fructose‐1,6‐diphosphatase of skeletal muscle by cross‐reinnervation. A histochemical and biochemical investigation of fatiguability‐related aspects. J. Neurol. Sci. 30: 1–11, 1976.
 134. Jolesz, F., and F. A. Sreter. Development, innervation, and activity‐pattern induced changes in skeletal muscle. Annu. Rev. Physiol. 43: 531–552, 1981.
 135. Jones, S. P., R. M. Ridge, and A. Rowlerson. The nonselective innervation of muscle fibres and mixed composition of motor units in a muscle of neonatal rat. J. Physiol. (Lond.) 386: 377–394, 1987.
 136. Jones, S. P., R. M. Ridge, and A. Rowlerson. Rat muscle during post‐natal development: evidence in favour of no interconversion between fast‐ and slow‐twitch fibres. J. Physiol. (Lond.) 386: 395–406, 1987.
 137. Kernell, D., and B. Zwaagstra. Input conductance axonal conduction velocity and cell size among hindlimb motoneurones of the cat. Brain Res. 204: 311–326, 1980.
 138. Keynes, R. J., and C. D. Stern. Segmentation in the vertebrate nervous system. Nature 310: 786–789, 1984.
 139. Keynes, R. J., R. V. Stirling, C. D. Stern, and D. Summer‐bell. The specificity of motor innervation of the chick wing does not depend upon the segmental origin of muscles. Development 99: 565–575, 1987.
 140. Klein, R., I. Silos‐Santiago, R. J. Smeyne, S. A. Lira, R. Brambilla, S. Bryant, L. Zhang, W. D. Snider, and M. Barbacid. Disruption of the neurotrophin‐3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature 368: 249–251, 1995.
 141. Lance‐Jones, C. Motoneuron axon guidance: development of specific projections to two muscles in the embryonic chick limb. Brain Behav. Evol. 31: 209–217, 1988.
 142. Lance‐Jones, C., and L. Landmesser. Motoneuron projection patterns to the chick hindlimb following early partial reversals of the spinal cord. J. Physiol. (Lond.) 301: 581–602, 1980.
 143. Lance‐Jones, C., and L. Landmesser. Motoneuron axon pathways in the developing hindlimb of the chick embryo. Proc. R. Soc. Lond. 214: 1–18, 1981.
 144. Lance‐Jones, C., and L. Landmesser. Motoneuron axon pathways in the embryonic chick hindlimb following early experimental manipulations of the spinal cord. Proc. R. Soc. Lond. 214: 19–52, 1981.
 145. Landmesser, L. The distribution of motoneurones supplying chick hind limb muscles. J. Physiol. (Lond.) 284: 371–389, 1978.
 146. Landmesser, L., and G. Pilar. Synaptic transmission and cell death during normal ganglionic development. J. Physiol. (Lond.) 241: 737–749, 1974.
 147. Landmesser, L. T. The generation of neuromuscular specificity. Annu. Rev. Neurosci. 3: 279–302, 1980.
 148. Larsson, L., L. Edstrom, B. Lindegren, L. Gorza, and S. Schiaffino. MHC composition and enzyme‐histochemical and physiological properties of a novel fast‐twitch motor unit type. Am. J. Physiol. 261: C93–101, 1991.
 149. Laskowski, M. B., and J. R. Sanes. Topographic mapping of motor pools onto skeletal muscles. J. Neurosci. 7: 252–260, 1987.
 150. Laskowski, M. B., and J. R. Sanes. Topographically selective reinnervation of adult mammalian skeletal muscles. J. Neurosci. 8: 3094–3099, 1988.
 151. Laufer, R., and J. P. Changeux. Calcitonin gene‐related peptide elevates cyclic AMP levels in chick skeletal muscle: Possible neurotrophic role for a coexisting neuronal messenger. EMBO J. 6: 901–906, 1987.
 152. Levi‐Montalcini, R. Developmental neurobiology and the natural history of nerve growth factor. Annu. Rev. Neurosci. 5: 341–362, 1982.
 153. Lewis, D. M., A. Rowlerson, and S. N. Webb. Motor units and immunohistochemistry of cat soleus muscle after long periods of cross‐reinnervation. J. Physiol. (Lond.) 325: 403–418, 1982.
 154. Lewis, S. E., P. Anderson, and D. F. Goldspink. The effects of calcium on protein turnover in skeletal muscles of the rat. Biochem. J. 204: 257–264, 1982.
 155. Lichtman, J. W., and R. J. Balice‐Gordon. Understanding synaptic competition in theory and in practice. J. Neurobiol. 21: 99–106, 1990.
 156. Lomo, T., and J. Rosenthal. Control of ACh sensitivity by muscle activity in the rat. J. Physiol. (Lond.) 221: 493–513, 1972.
 157. Luff, A. R. Dynamic properties of fast and slow skeletal muscles in the cat and rat following cross‐reinnervation. J. Physiol. (Lond.) 248: 83–96, 1975.
 158. Lumsden, A. G., and A. M. Davies. Chemotropic effect of specific target epithelium in the developing mammalian nervous system. Nature 323: 538–539, 1986.
 159. Macintosh, B. R., M. C. Roberge, and P. F. Gardiner. Absence of staircase following disuse in rat gastrocnemius muscle. Can. J. Physiol. Pharmacol. 66: 707–713, 1988.
 160. Margreth, A., G. Salviati, and I. Mussini. Biochemical changes in slow muscle by reinnervation with fast nerve fibres. In: Clinical Studies in Myology, edited by B. A. Kakulas. Amsterdam: Excerpta Medica, 1973, p. 337–345.
 161. Martin, D. P., R. E. Schmidt, P. S. DiStefano, O. H Lowry, J. G. Carter, and E. Johnson, Jr.. Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J. Cell Biol. 106: 829–844, 1988.
 162. Martinou, J. C., D. L. Falls, G. D. Fischbach, and J. P. Merlie. Acetylcholine receptor‐inducing activity stimulates expression of the epsilon‐subunit gene of the muscle acetylcholine receptor. Proc. Natl. Acad. Sci. U. S. A. 88: 7669–7673, 1991.
 163. Martinou, J. C., and J. P. Merlie. Nerve‐dependent modulation of acetylcholine receptor epsilon‐subunit gene expression. J. Neurosci. 11: 1291–1299, 1991.
 164. McMahan, U. J. The agrin hypothesis. Cold Spring Harb. Symp. Quant. Biol. 55: 407–418, 1990.
 165. McManaman, J. L., R. W. Oppenheim, D. Prevette, and D. Marchetti. Rescue of motoneurons from cell death by a purified skeletal muscle polypeptide: effects of the ChAT development factor, CDF. Neuron 4: 891–898, 1990.
 166. Menesini Chen, M. G., J. S. Chen, and R. Levi‐Montalcini. Sympathetic nerve fibers ingrowth in the central nervous system of neonatal rodent upon intracerebral NGF injections. Arch. Ital. Biol. 116: 53–84, 1978.
 167. Merlie, J. P., and J. R. Sanes. Concentration of acetylcholine receptor mRNA in synaptic regions of adult muscle fibres. Nature 317: 66–68, 1985.
 168. Miller, J. B., M. T. Crow, and F. E. Stockdale. Slow and fast myosin heavy chain content defines three types of myotubes in early muscle cell cultures. J. Cell Biol. 101: 1643–1650, 1985.
 169. Miller, J. B., and F. E. Stockdale. Developmental origins of skeletal muscle fibers: clonal analysis of myogenic cell lineages based on expression of fast and slow myosin heavy chains. Proc. Natl. Acad. Sci. U. S. A. 83: 3860–3864, 1986.
 170. Miyata, H., and Y. Kawai. Relationship between soma diameter and oxidative enzyme activity of alpha‐motoneurons. Brain Res. 581: 101–107, 1992.
 171. Miyata, Y., and K. Yoshioka. Selective elimination of motor nerve terminals in the rat soleus muscle during development. J. Physiol. (Land.) 309: 631–646, 1980.
 172. Mjaatvedt, A. E., and M. T. Wong‐Riley. Double‐labeling of rat alpha‐motoneurons for cytochrome oxidase and retrogradely transported [3H]WGA. Brain Res. 368: 178–182, 1986.
 173. Mommaerts, W. F., K. Seraydarian, M. Suh, C. J. Kean, and A. J. Buller. The conversion of some biochemical properties of mammalian skeletal muscles following cross‐rein‐nervation. Exp. Neurol. 55: 637–653, 1977.
 174. Muntener, M., A. M. Rowlerson, M. W. Berchtold, and C. W. Heizmann. Changes in the concentration of the calcium‐binding parvalbumin in cross‐reinnervated rat muscles. Comparison of biochemical with physiological and histochemical parameters. J. Biol. Chem. 262: 465–469, 1987.
 175. Narusawa, M., R. B. Fitzsimons, S. Izumo, B. Nadal‐Ginard, N. A. Rubinstein, and A. M. Kelly. Slow myosin in developing rat skeletal muscle. J. Cell Biol. 104: 447–459, 1987.
 176. Navarrette, R., and G. Vrbova. Activity‐dependent interactions between motoneurones and muscles: their role in the development of the motor unit. Prog. Neurobiol. 41: 93–124, 1993.
 177. Navarrette, R., K. D. Walton, and R. R. Llinas. Postnatal changes in the electrical properties of muscle‐identified rat motoneurons: an in vitro study. Soc. Neurosci. Abstr. 13: 1060, 1988.
 178. Neville, C. M., M. Schmidt, and J. Schmidt. Response of myogenic determination factors to cessation and resumption of electrical activity in skeletal muscle: a possible role for myogenin in denervation supersensitivity. Cell. Mol. Neurobiol. 12: 511–527, 1992.
 179. O'Brien, R. A., A. J. Ostberg, and G. Vrbova. Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle. J. Physiol. (Lond.) 282: 571–582, 1978.
 180. O'Donovan, M. J., M. J. Pinter, R. P. Dum, and R. E. Burke. Kinesiological studies of self‐ and cross‐reinnervated FDL and soleus muscles in freely moving cats. J. Neurophysiol. 54: 852–866, 1985.
 181. Okada, A., S. Furber, N. Okado, S. Homma, and R. W. Oppenheim. Cell death of motoneurons in the chick embryo spinal cord. X. Synapse formation on motoneurons following the reduction of cell death by neuromuscular blockade. J. Neurobiol. 20: 219–233, 1989.
 182. Olson, E. N. Interplay between proliferation and differentiation within the myogenic lineage. Dev. Biol. 154: 261–272, 1992.
 183. Oppenheim, R. W. Cell death during development of the nervous system. Annu. Rev. Neurosci. 14: 453–501, 1991.
 184. Oppenheim, R. W., I. W. Chu‐Wang, and J. L. Maderdrut. Cell death of motoneurons in the chick embryo spinal cord. III. The differentiation of motoneurons prior to their induced degeneration following limb‐bud removal. J. Comp. Neurol. 177: 87–111, 1978.
 185. Oppenheim, R. W., D. Prevette, M. Tytell, and S. Homma. Naturally occurring and induced neuronal death in the chick embryo in vivo rquires protein and RNA synthesis: evidence for the role of cell death genes. Dev. Biol. 138: 104–113, 1990.
 186. Osterlund, M., B. Fontaine, A. Devillers‐Thiery, B. Geoffroy, and J. P. Changeux. Acetylcholine receptor expression in primary cultures of embryonic chick myotubes—I. Discoordinate regulation of alpha‐, gamma‐ and delta‐subunit gene expression by calcitonin gene‐related peptide and by muscle electrical activity. Neuroscience 32: 279–287, 1989.
 187. Page, S., J. B. Miller, J. X. DiMario, E. J. Hager, A. Moser, and F. E. Stockdale. Developmentally regulated expression of three slow isoforms of myosin heavy chain: diversity among the first fibers to form in avian muscle. Dev. Biol. 154: 118–128, 1992.
 188. Pearson, J. K., and D. W. Sickles. Enzyme activity changes in rat soleus motoneurons and muscle after synergist ablation. J. Appl. Physiol. 63: 2301–2308, 1987.
 189. Penny, J. E., J. R. Kukums, J. H. Tyrer, and M. J. Eadie. Quantitative oxidative enzyme histochemistry of the spinal cord. Part 2. Relation of cell size and enzyme activity to vulnerability to ischaemia. J. Neurol. Sci. 26: 187–192, 1975.
 190. Peter, J. B., R. J. Barnard, V. R. Edgerton, C. A. Gillespie, and K. E. Stempel. Metabolic profiles of three fiber types of skeletal muscle in guinea pigs and rabbits. Biochemistry 11: 2627–2633, 1972.
 191. Pette, D., and R. S. Staron. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev. Physiol. Biochem. Pharmacol. 116: 1–76, 1990.
 192. Pette, D., and G. Vrbova. Neural control of phenotypic expression in mammalian muscle fibers. Muscle Nerve 8: 676–689, 1985.
 193. Pierotti, D. J., R. R. Roy, S. C. Bodine‐Fowler, J. A. Hodgson, and V. R. Edgerton. Mechanical and morphological properties of chronically inactive cat tibialis anterior motor units. J. Physiol. (Lond.) 444: 175–192, 1991.
 194. Pierotti, D. J., R. R. Roy, J. A. Hodgson, and V. R. Edgerton. Level of independence of motor unit properties from neuromuscular activity. Muscle Nerve 17: 1324–1335, 1994.
 195. Pittman, R., and R. W. Oppenheim. Cell death of motoneurons in the chick embryo spinal cord. IV. Evidence that a functional neuromuscular interaction is involved in the regulation of naturally occurring cell death and the stabilization of synapses. J. Comp. Neurol. 187: 425–446, 1979.
 196. Prewitt, M. A., and B. Salafsky. Effect of cross innervation on biochemical characteristics of skeletal muscles. Am. J. Physiol. 213: 295–300, 1967.
 197. Reichmann, H., T. Srihari, and D. Pette. Ipsi‐ and contralateral fibre transformations by cross‐reinnervation. A principle of symmetry. Pflugers Arch. 397: 202–208, 1983.
 198. Reiness, C. G., and C. B. Weinberg. Metabolic stabilization of acetylcholine receptors at newly formed neuromuscular junctions in rat. Dev. Biol. 84: 247–254, 1981.
 199. Reist, N. E., M. J. Werle, and U. J. McMahan. Agrin released by motor neurons induces the aggregation of acetylcholine receptors at neuromuscular junctions. Neuron 8: 865–868, 1992.
 200. Ribchester, R. R. Activity‐dependent and ‐independent synaptic interactions during reinnervation of partially denervated rat muscle. J. Physiol. (Lond.) 401: 53–75, 1988.
 201. Ribchester, R. R., and T. Taxt. Repression of inactive motor nerve terminals in partially denervated rat muscle after regeneration of active motor axons. J. Physiol. (Lond.) 347: 497–511, 1984.
 202. Ridge, R. M., and W. J. Betz. The effect of selective, chronic stimulation on motor unit size in developing rat muscle. J Neurosci. 4: 2614–2620, 1984.
 203. Riley, D. A. Spontaneous elimination of nerve terminals from the endplates of developing skeletal myofibers. Brain Res. 134: 279–285, 1977.
 204. Robbins, N., G. Karpati, and W. K. Engel. Histochemical and contractile properties in the cross‐innervated guinea pig soleus muscle. Arch. Neurol. 20: 318–329, 1969.
 205. Ross, J. J., M. J. Duxson, and A. J. Harris. Neural determination of muscle fibre numbers in embryonic rat lumbrical muscles. Development 100: 395–409, 1987.
 206. Rossi, S. G., and R. L. Rotundo. Cell surface acetylcholinesterase molecules on multinucleated myotubes are clustered over the nucleus of origin. J. Cell Biol. 119: 1657–1667, 1992.
 207. Roy, R. R., K. M. Baldwin, and V. R. Edgerton. The plasticity of skeletal muscle: effects of neuromuscular activity. Exerc. Sport Sci. Rev. 19: 269–312, 1991.
 208. Roy, R. R., K. M. Baldwin, R. D. Sacks, L. Eldridge, and V. R. Edgerton. Mechanical and metabolic properties after prolonged inactivation and/or cross‐reinnervation of cat soleus. Med. Sci. Sports Exerc. 19: 550, 1987.
 209. Roy, R. R., J. A. Hodgson, S. D. Lauretz, D. J. Pierotti, R. J. Grayek, and V. R. Edgerton. Chronic spinal cord‐injured cats: surgical procedures and management. Lab. Anim. Sci. 42: 335–343, 1992.
 210. Roy, R. R., D. L. Hutchison, D. J. Pierotti, J. A. Hodgson, and V. R. Edgerton. EMG patterns of rat ankle extensors and flexors during treadmill locomotion and swimming. J. Appl. Physiol. 70: 2522–2529, 1991.
 211. Roy, R. R., D. J. Pierotti, V. Flores, W. Rudolph, and V. R. Edgerton. Fibre size and type adaptations to spinal isolation and cyclical passive stretch in cat hindlimb. J. Anat. 180: 491–499, 1992.
 212. Salmons, S., and J. Henriksson. The adaptive response of skeletal muscle to increased use. Muscle Nerve 4: 94–105, 1981.
 213. Sanes, J. R., Y. R. Johnson, P. T. Kotzbauer, J. Mudd, T. Hanley, J. C. Martinou, and J. P. Merlie. Selective expression of an acetylcholine receptor‐lacZ transgene in synaptic nuclei of adult muscle fibers. Development 113: 1181–1191, 1991.
 214. Sassoon, D. A. Myogenic regulatory factors: dissecting their role and regulation during vertebrate embryogenesis. Dev. Biol. 156: 11–23, 1993.
 215. Schiaffino, S., L. Gorza, G. Pitton, L. Saggin, S. Ausoni, S. Sartore, and T. Lomo. Embryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle. Dev. Biol. 127: 1–11, 1988.
 216. Schuetze, S. M., and L. W. Role. Developmental regulation of nicotinic acetylcholine receptors. Annu. Rev. Neurosci. 10: 403–457, 1987.
 217. Schwab, M. E., J. P. Kapfhammer, and C. E. Bandtlow. Inhibitors of neurite growth. Annu. Rev. Neurosci. 16: 565–595, 1993.
 218. Secrist, D. J., and W. G. Kerrick. Associated changes in Ca2+ and Sr2+ activation properties and fiber proteins in cross‐reinnervated rabbit soleus. Pflugers Arch. 384: 219–229, 1980.
 219. Sekiya, S., S. Homma, Y. Miyata, and M. Kuno. Effects of nerve growth factor on differentiation of muscle spindles following nerve lesion in neonatal rats. J. Neurosci. 6: 2019–2025, 1986.
 220. Shyng, S. L., and M. M. Salpeter. Effect of reinnervation on the degradation rate of junctional acetylcholine receptors synthesized in denervated skeletal muscles. J. Neurosci. 10: 3905–3915, 1990.
 221. Sickles, D. W., and R. E. McLendon. Metabolic variation among rat lumbrosacral alpha‐motoneurons. Histochemistry 79: 205–217, 1983.
 222. Sickles, D. W., and T. G. Oblak. A horseradish peroxidase labeling technique for correlation of motoneuron metabolic activity with muscle fiber types. J. Neurosci. Methods 7: 195–201, 1983.
 223. Sickles, D. W., and T. G. Oblak. Metabolic variation among alpha‐motoneurons innervating different muscle‐fiber types. I. Oxidative enzyme activity. J. Neurophysiol. 51: 529–537, 1984.
 224. Sickles, D. W., T. G. Oblak, and J. Scholer. Hyperthyroidism selectively increases oxidative metabolism of slow‐oxidative motor units. Exp. Neurol. 97: 90–105, 1987.
 225. Simon, A. M., P. Hoppe, and S. J. Burden. Spatial restriction of AChR gene expression to subsynaptic nuclei. Development 114: 545–553, 1992.
 226. Snider, W. D., and E. Johnson, Jr.. Neurotrophic molecules. Ann. Neurol. 26: 489–506, 1989.
 227. Spector, S. A. Trophic effects on the contractile and histochemical properties of rat soleus muscle. J Neurosci. 5: 2189–2196, 1985.
 228. Sreter, F. A., and J. Gergely. The effect of cross reinnervation on the synthesis of myosin light chains. Biochem. Biophys. Res. Commun. 56: 84–89, 1974.
 229. Sreter, F. A., A. R. Luff, and J. Gergely. Effect of cross‐reinnervation on physiological parameters and on properties of myosin and sarcoplasmic reticulum of fast and slow muscles of the rabbit. J. Gen. Physiol. 66: 811–821, 1975.
 230. St‐Pierre, D. M., D. Leonard, and P. F. Gardiner. Recovery of muscle from tetrodotoxin‐induced disuse and the influence of daily exercise. 1. Contractile properties. Exp. Neurol. 98: 472–488, 1987.
 231. St‐Pierre, D. M., D. Leonard, R. Houle, and P. F. Gardiner. Recovery of muscle from tetrodotoxin‐induced disuse and the influence of daily exercise. 2. Muscle enzymes and fatigue characteristics. Exp. Neurol. 101: 327–346, 1988.
 232. Steinbach, J. H., D. Schubert, and L. Eldridge. Changes in cat muscle contractile proteins after prolonged muscle inactivity. Exp. Neurol. 67: 655–669, 1980.
 233. Stockdale, F. E. Myogenic cell lineages. Dev. Biol. 154: 284–298, 1992.
 234. Sypert, G W., and J. B. Munson. Basis of segmental motor control: motoneuron size or motor unit type? Neurosurgery 8: 608–621, 1981.
 235. Tanaka, H. Chronic application of curare does not increase the level of motoneuron survival‐promoting activity in limb muscle extracts during the naturally occurring motoneuron cell death period. Dev. Biol. 124: 347–357, 1987.
 236. Tanaka, H., and L. T. Landmesser. Cell death of lumbosacral motoneurons in chick, quail, and chick‐quail chimera embryos: a test of the quantitative matching hypothesis of neuronal cell death. J. Neurosci. 6: 2889–2899, 1986.
 237. Tang, J., L. Landmesser, and U. Rutishauser. Polysialic acid influences specific pathfinding by avian motoneurons. Neuron 8: 1031–1044, 1992.
 238. Tessier‐Lavigne, M., M. Placzek, A. G. Lumsden, J. Dodd, and T. M. Jessell. Chemotropic guidance of developing axons in the mammalian central nervous system. Nature 336: 775–778, 1988.
 239. Thomas, P. E., and K. W. Ranatunga. Factors affecting muscle fiber transformation in cross‐reinnervated muscle. Muscle Nerve 16: 193–199, 1993.
 240. Thompson, W. Synapse elimination in neonatal rat muscle is sensitive to pattern of muscle use. Nature 302: 614–616, 1983.
 241. Thompson, W., D. P. Kuffler, and J. K. Jansen. The effect of prolonged, reversible block of nerve impulses on the elimination of polyneuronal innervation of new‐born rat skeletal muscle fibers. Neuroscience 4: 271–281, 1979.
 242. Thompson, W. J. Lack of segmental selectivity in elimination of synapses from soleus muscle of new‐born rats. J. Physiol. (Lond.) 335: 343–352, 1983.
 243. Thompson, W. J. Activity and synapse elimination at the neuromuscular junction. Cell. Mol. Neurobiol. 5: 167–182, 1985.
 244. Thompson, W. J., K. Condon, and S. H. Astrow. The origin and selective innervation of early muscle fiber types in the rat. J. Neurobiol. 21: 212–222, 1990.
 245. Thompson, W. J., and J. K. S. Jansen. The extent of sprouting of remaining motor units in partly denervated immature and adult rat soleus muscle. Neuroscience 2: 523–535, 1977.
 246. Thompson, W. J., L. A. Sutton, and D. A. Riley. Fibre type composition of single motor units during synapse elimination in neonatal rat soleus muscle. Nature 309: 709–711, 1984.
 247. Tosney, K. W. Somites and axon guidance. Scanning Microsc. 2: 427–442, 1988.
 248. Tosney, K. W., and L. T. Landmesser. Pattern and specificity of axonal outgrowth following varying degrees of chick limb bud ablation. J. Neurosci. 4: 2518–2527, 1984.
 249. Toutant, J. P., and J. Massoulie. Acetylcholinesterase. In: Mammalian Ectoenzymes, edited by A. J. Kenny and A. J. Turner. New York: Elsevier Science Publishers, 1987, p. 289–328.
 250. Tower, S. S. Function and structure in the chronically isolated lumbosacral spinal cord of the dog. J. Comp. Neurol. 67: 109–131, 1937.
 251. Tsay, H. J., and J. Schmidt. Skeletal muscle denervation activates acetylcholine receptor genes. J. Cell Biol. 108: 1523–1526, 1989.
 252. Tseng, B. S., C. E. Kasper, and V. R. Edgerton. Cytoplasm‐to‐myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers. Cell Tissue Res. 275: 39–49, 1994.
 253. Turcotte, R., R. Panenic, and P. F. Gardiner. TTX‐induced muscle disuse alters CA2+ activation characteristics of myofibril ATPase. Comp. Biochem. Physiol. A 100: 183–186, 1991.
 254. Uchida, S., H. Yamamoto, S. Iio, N. Matsumoto, X. B. Wang, N. Yonehara, Y. Imai, R. Inoki, and H. Yoshida. Release of calcitonin gene‐related peptide‐like immunoreactive substance from neuromuscular junction by nerve excitation and its action on striated muscle. J. Neurochem. 54: 1000–1003, 1990.
 255. Unguez, G. A., S. Bodine‐Fowler, R. R. Roy, D. J. Pierotti, and V. R. Edgerton. Evidence of incomplete neural control of motor unit properties in cat tibialis anterior after self‐reinnervation. J. Physiol. (Lond.) 472: 103–125, 1993.
 256. Usdin, T. B., and G. D. Fischbach. Purification and characterization of a polypeptide from chick brain that promotes the accumulation of acetylcholine receptors in chick myotubes. J. Cell Biol. 103: 493–507, 1986.
 257. Villar, M. J., M. Roa, M. Huchet, T. Hokfelt, J. P. Changeux, J. Fahrenkrug, J. C. Brown, M. Epstein, and L. Hersh. Immunoreactive calcitonin gene‐related peptide, vasoactive intestinal polypeptide and somatostatin: distribution in developing chicken spinal cord motoneurons and role in regulation of muscle acetylcholine receptor synthesis. Eur. J. Neurosci. 1: 269–287, 1989.
 258. Vivarelli, E., W. E. Brown, R. G. Whalen, and G. Cossu. The expression of slow myosin during mammalian somitogenesis and limb bud differentiation. J. Cell Biol. 107: 2191–2197, 1988.
 259. Wan, K. K., and R. J. Boegman. Calcium uptake by muscle sarcoplasmic reticulum following neural application of batrachotoxin or tetrodotoxin. FEBS Lett. 112: 163–167, 1980.
 260. Wan, K. K., and R. J. Boegman. Response of rat skeletal muscle to neural application of batrachotoxin or tetrodotoxin: effect on soluble proteins. Exp. Neurol. 74: 447–457, 1981.
 261. Windhorst, U., T. M. Hamm, and D. G. Stuart. On the function of muscle and reflex partitioning. Behav. Brain Sci. 12: 629–681, 1989.
 262. Witzemann, V., B. Barg, M. Criado, E. Stein, and B. Sakmann. Developmental regulation of five subunit specific mRNAs encoding acetylcholine receptor subtypes in rat muscle. FEBS Lett. 242: 419–424, 1989.
 263. Witzemann, V., and B. Sakmann. Differential regulation of MyoD and myogenin mRNA levels by nerve induced muscle activity. FEBS Lett. 282: 259–264, 1991.
 264. Yamada, S., N. Buffinger, J. DiMario, and R. C. Strohman. Fibroblast growth factor is stored in fiber extracellular matrix and plays a role in regulating muscle hypertrophy. Med. Sci. Sports Exerc. 21: S173–S180, 1989.
 265. Ziskind‐Conhaim, L. Electrical properties of motoneurons in the spinal cord of rat embryos. Dev. Biol. 128: 21–29, 1988.
 266. Zwaagstra, B., and D. Kernell. The duration of after‐hyperpolarization in hindlimb alpha motoneurons of different sizes in the cat. Neurosci. Lett. 19: 303–307, 1980.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

V. R. Edgerton, S. Bodine‐Fowler, R. R. Roy, A. Ishihara, J. A. Hodgson. Neuromuscular Adaptation. Compr Physiol 2011, Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems: 54-88. First published in print 1996. doi: 10.1002/cphy.cp120102