Elimination of motor nerve terminals in neonatal mice expressing a gene for slow wallerian degeneration (C57Bl/Wlds).

Abstract

Degeneration of motor terminals after nerve section occurs much more slowly than normal in young adult mice of the C57Bl/Wlds strain. This observation prompted us to re-examine the possible role of degeneration and intrinsic axon withdrawal during neonatal synapse elimination. Polyneuronal innervation was assayed by two methods: intracellular recording of end-plate potentials in cut-muscle fibre preparations of isolated hemidiaphragm and soleus muscles; and in silver-stained preparations of triangularis sterni and transversus abdominis muscle fibres. No differences in the rate of synapse elimination were detected in unoperated Wlds compared with CBA, C3H/HE and BALB/c mice. At 3 days of age, > 80% of fibres were polyneuronally innervated. By 7 days this declined to approximately 20% of hemidiaphragm, 50% of triangularis sterni and 60% of soleus fibres. Nearly all fibres were mononeuronally innervated by 15 days. The mean number of terminals per triangularis sterni muscle fibre 7 days after birth was 1.55 +/- 0.07 in Wlds and 1.56 +/- 0.09 in wild-type mice. Three to 4 days after sciatic nerve section, near-normal numbers of motor units were evident in isometric tension recordings of the soleus muscle, and intracellular recordings revealed many polyneuronally innervated fibres. Mononeuronally and polyneuronally innervated fibres were also observed in silver-stained preparations of soleus and transversus abdominis muscles made 3-4 days after sciatic or intercostal nerve section. We conclude (i) that the Wlds gene has no direct impact on the normal rate of postnatal synapse elimination, (ii) that Wallerian degeneration and synapse elimination must occur by distinct and different mechanisms, and (iii) that muscle fibres are able to sustain polyneuronal synaptic inputs even after motor axons have become disconnected from their cell bodies.