Hind, Angela Marie; (1991) The importance of early nerve-muscle interactions on muscle development. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

During early postnatal development, individual muscle fibres are contacted by several axons at a single endplate. The excess synaptic input is eliminated during the first 3 weeks of postnatal life, so that only a single axon remains in contact with each endplate. Neuromuscular activity is important for this event to occur. Here evidence is provided in support of the hypothesis that the process of elimination involves a calcium-activated neutral protease (CANP) which degrades the neurofilament structure of axons which are being retracted. The second part of this thesis addresses the question of the importance of target activity in the formation and establishment of the normal distribution of innervation in the slow soleus muscle. The soleus muscle is innervated by axons emanating from the L4 and L5 spinal roots. At birth there is an overlap of innervation between the L4 and L5 axons. As polyneuronal innervation is eliminated there is a disproportionate reduction in the territory of the L4 axons relative to the L5 axons. Following temporary paralysis at birth, the adult soleus muscle demonstrates a reduction in tension output and muscle fibre numbers. This reduction is almost solely due to loss of muscle fibres innervated by L5 axons. Thus, target activity is essential in the early postnatal period for the development of the normal distribution of innervation. The extent to which target activity affects the normal development of the fast muscles, tibialis anterior (TA) and extensor digitorum longus (EDL) was also investigated. Nerve-muscle interactions were prevented shortly after birth and the effects on muscle development following subsequent nerve injury were investigated. Nerve crush at 5 days produced a significant loss of tension, so that TA and EDL muscles produced 50-55% of the force of controls. If nerve crush was preceeded by bungarotoxin paralysis the force produced by the TA muscle was further reduced so that it produced only 38% of tension compared to control. EDL muscles were not affected by the paralysis and produced approximately 50% of tension of controls. It therefore appears that the TA muscle is more significantly affected by interuption in nerve-muscle contacts in early development than the EDL muscle. The results presented in this thesis illustrate the critical interdependence of nerve and muscle in early postnatal development and that the interaction between the motor nerve and the muscle has a major influence on the development of the neuromuscular system.

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