Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, C111

Oral Communications

Motor Unit Size-Dependent Intrinsic Withdrawal of Neuromuscular Synapses During Postnatal Development of Mouse Muscle.

A. Teriakidis1, D. J. Willshaw2, R. R. Ribchester3

1. Neuroinformatics DTC, University of Edinburgh, Edinburgh, United Kingdom. 2. Institute for Adaptive Neural Computation, University of Edinburgh, Edinburgh, United Kingdom. 3. Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, United Kingdom.

At birth every muscle fibre has functional synaptic inputs from multiple motor neurons, all but one of which are eliminated. Synapse elimination is driven by competition between synapses co-innervating a muscle fibre (Betz et al., 1980). However, an unresolved question is whether synapse elimination can occur in the absence of competition. Some evidence suggests that ‘intrinsic withdrawal’ of synapses continues at some neuromuscular junctions (NMJs) after partial denervation at birth (Fladby and Jansen; 1988), leaving some endplates uninnervated. We have re-examined the question of ‘intrinsic withdrawal’ by directly measuring motor unit (MU) size in transgenic mice expressing yellow fluorescent protein in motor neurons (thy1.2:YFP). We used confocal microscopy to determine MU sizes in the 4th deep lumbrical (4DL) muscle of unoperated control mice, adult mice whose muscles had been partially denervated at birth by bilateral tibial nerve cuts (neonates anaesthetised by chilling) leaving a single innervating axon through the sural nerve (AwPD) and neonates. We found that the average MU size was significantly smaller in control mice (54 ± 11, n = 29, mean ± SD) than in neonates (137 ± 63, n = 10, p<0.001, Tukey HSD) and in AwPD (103 ± 29, n = 10, p<0.001, Tukey HSD) though the difference between neonates and AwPD only approached significance (p=0.058, Tukey HSD). While the smallest MU size in those two groups was approximately the same, there were several MUs that were larger in the neonates than the maximum MU size in the AwPD, suggesting that only motor units above a certain size may lose synapses in the absence of competition. The present data suggest that there is an intrinsic limit to the number of synapses a motor neuron can sustain and that this number may decline as axons and muscle fibres grow. We have been modifying a computational model of synapse elimination to examine the effect of growth on MU size (Rasmussen & Willshaw, 1993).

Where applicable, experiments conform with Society ethical requirements