| Summary: | The thesis presents contributions to the field of neuromuscular synaptic plasticity. Synaptic remodelling brings about changes in convergence and divergence in many different parts of the nervous system during development. Neuromuscular junctions have proved to be accessible synapses in which to describe and explain the mechanisms. During development, muscle fibres initially receive convergent, polyneuronal innervation (π) by axons arising from different motor neurones. The characteristic mononeuronal innervation (µ) pattern of adult muscle is achieved by synapse elimination, a process of weakening of synaptic strength followed by withdrawal of synaptic boutons, until all but one of the motor neuron inputs to an endplate is lost. Similar hyperinnervation and elimination occur in adult muscle after nerve injury, collateral sprouting and regeneration. These processes are strongly influenced by activity, apparently in accordance with Hebbian rules of synaptic plasticity. But how decisive is activity in ultimately determining the pattern of neuromuscular connectivity? The amount of sprouting is increased and the rate of synapse elimination is decreased when muscle activity is blocked. Sprouts regress and synapse elimination resumes when muscles are stimulated, or once normal activity is restored. Selectively blocking or restoring activity in some motor neurones but not others supplying a π-junction gives a competitive advantage to the more active neuromuscular synapses. However, activity is not sufficient to effect synapse elimination because many muscle fibres retain π-junctions after activity resumes following a period of paralysis. Nor is activity strictly necessary, because – paradoxically – synapse elimination continues at some motor endplates even when muscles are completely paralysed. Competition for neurotrophic factors may play an important role in determining the outcome of synapse elimination, but factors intrinsic to the motor neurone, perhaps involving the selective trafficking of maintenance factors along specific axon collaterals, appear to be important also. In each motor neurone, synapses are eliminated or strengthened asynchronously.
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