Slowing of synapse elimination by alpha-bungarotoxin superfusion of the neonatal rabbit soleus muscle.

To examine the role of postsynaptic activity in regulating the rate of neuromuscular synapse elimination, contractile activity of neonatal rabbit soleus muscles was decreased by chronic superfusion of alpha-bungarotoxin (alpha-BGT) over their surfaces. Superfusion was begun at 6 days postnatal and continued for a variable duration (2 to 5 days) before muscles were analyzed. The percentage of polyinnervated fibers was assessed both physiologically and anatomically for alpha-BGT-treated muscles and their contralateral muscles, in addition to normal and control muscles of the same age. Within muscles exposed to alpha-BGT, polyinnervation was significantly greater than that for muscles from each of the control groups. The anatomical assay further revealed that the retention of polyinnervation in alpha-BGT-treated muscles was most pronounced near the muscle's surface, although end plates at the center were also affected. This finding, coupled with evidence that only a small percentage of the muscle fibers were completely inactivated, suggests that the activity block was also most pronounced near the surface and relatively low at the muscle's center. The percentage of end plates at which synapse elimination was delayed was greater than the estimated percentage whose activity was completely blocked, suggesting that synapse loss was slowed even in muscle fibers retaining some postsynaptic activity. These observations indicate that the rate of synapse elimination depends on the levels of functional acetylcholine receptors. This process could be mediated in a graded fashion by changes in postsynaptic activity (subthreshold or suprathreshold) or by a nonelectrical effect of blocking postsynaptic receptors.

[1]  E. Callaway,et al.  Differential loss of neuromuscular connections according to activity level and spinal position of neonatal rabbit soleus motor neurons , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  R. O'brien,et al.  Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle. , 1978, The Journal of physiology.

[3]  M. Salpeter,et al.  Absence of [125I] alpha-bungarotoxin binding to motor nerve terminals of frog, lizard and mouse muscle , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  J. Maunsell,et al.  Effects of motor unit size on innervation patterns in neonatal mammals , 1980, Experimental Neurology.

[5]  J. Jansen,et al.  The innervation of skeletal muscles in chickens curarized during early development , 1983, Journal of neurocytology.

[6]  M. Karnovsky,et al.  A "DIRECT-COLORING" THIOCHOLINE METHOD FOR CHOLINESTERASES , 1964, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[7]  L. Swanson,et al.  Use of monoclonal antibodies to study acetylcholine receptors from electric organs, muscle, and brain and the autoimmune response to receptor in myasthenia gravis. , 1983, Cold Spring Harbor symposia on quantitative biology.

[8]  W. Thompson Synapse elimination in neonatal rat muscle is sensitive to pattern of muscle use , 1983, Nature.

[9]  P. Redfern Neuromuscular transmission in new‐born rats , 1970, The Journal of physiology.

[10]  R. H. PITTMAN,et al.  Neuromuscular blockade increases motoneurone survival during normal cell death in the chick embryo , 1978, Nature.

[11]  R. O'brien,et al.  Protease inhibitors reduce the loss of nerve terminals induced by activity and calcium in developing rat soleus muscles in vitro , 1984, Neuroscience.

[12]  J. K. S. Jansen,et al.  The effect of prolonged, reversible block of nerve impulses on the elimination of polyneuronal innervation of new-born rat skeletal muscle fibers , 1979, Neuroscience.

[13]  Edward M. Callaway,et al.  Competition favouring inactive over active motor neurons during synapse elimination , 1987, Nature.

[14]  J. Soha,et al.  Synapse elimination by fiber type and maturational state in rabbit soleus muscle. , 1987, Developmental biology.

[15]  A. Pestronk,et al.  Motor nerve terminal outgrowth and acetylcholine receptors: inhibition of terminal outgrowth by alpha-bungarotoxin and anti-acetylcholine receptor antibody , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  R. L. Holland,et al.  Restoration of focal multiple innervation in rat muscles by transmission block during a critical stage of development , 1981, The Journal of physiology.

[17]  S. W. Jones Presynaptic mechanisms at vertebrate neuromuscular junctions , 1987 .

[18]  J. Caldwell,et al.  The effects of deafferentation and spinal cord transection on synapse elimination in developing rat muscles. , 1983, The Journal of physiology.

[19]  M. Duxson,et al.  The effect of postsynaptic block on development of the neuromuscular junction in postnatal rats , 1982, Journal of neurocytology.

[20]  M. C. Brown,et al.  Postnatal growth of motor nerve terminals in muscles of the mouse , 1985, Journal of neurocytology.

[21]  D. V. Essen,et al.  Regional differences in the timing of synapse elimination in skeletal muscles of the neonatal rabbit , 1979, Brain Research.

[22]  J. Changeux,et al.  Consequences of tenotomy on the evolution of multiineervation in developing rat soleus muscle , 1975, Brain Research.

[23]  A L Connold,et al.  Effect of low calcium and protease inhibitors on synapse elimination during postnatal development in the rat soleus muscle. , 1986, Brain research.

[24]  A. Pestronk,et al.  A new stain for quantitative measurement of sprouting at neuromuscular junctions , 1978, Muscle & nerve.

[25]  R. L. Holland,et al.  An assessment of the spread of the signal for terminal sprouting within and between muscles , 1981, Brain Research.

[26]  Gerta Vrbová,et al.  The role of muscle activity in the differentiation of neuromuscular junctions in slow and fast chick muscles , 1978, Journal of neurocytology.

[27]  David C. Van Essen,et al.  Neuromuscular Synapse Elimination , 1982 .