Short- and long-term effects of paralysis on the motor innervation of two different neonatal mouse muscles.

Abstract

1. A study was made of short- and long-term effects of paralysis induced by type A botulinum toxin on the development of innervation of mouse muscles. The toxin was injected locally over the tensor fasciae latae (t.f.l.) and gluteus muscles at various times after birth, and the innervation was later examined by intracellular recording and by a histological technique using a reduced silver stain for axons.2. Paralysis induced at 0-4 days of age delayed but did not prevent the eventual elimination of nearly all focal multiple innervation in gluteus muscle fibres, whereas in t.f.l. up to 50% of the fibres remained focally innervated by more than one axon for at least 120 days. There was an associated reduction in the number of muscle fibres in t.f.l. of between 50 and 70%. The biggest reduction in the number of gluteus fibres was under 40%.3. In the t.f.l., paralysis begun at 6-9 days caused the extent of single-site polyneuronal innervation to increase above the level existing at the time of paralysis. Histologically this increase was seen to be due at least in part to the stimulation of nodal sprout growth from a limited number of nodes.4. Motor nerve terminal sprouts were evoked by paralysis at all ages. In mice injected before 4 days of age recovery from the toxin occurred rapidly and without the formation of ectopic synapses by sprouted motor terminals; however, intrafusal motor nerves also sprouted and established a permanent ectopic innervation on surrounding extrafusal muscle fibres.5. The following conclusions are drawn. (a) In some but not all muscles, neonatally induced paralysis can not only temporarily halt elimination of polyneuronal innervation but actually lead to an increase; it is suggested tentatively that this occurs only during the neonatal period because of the availability at that time of endoneurial pathways associated with normal polyneuronal innervation, rather than because of any special neuronal growth potential then. (b) Permanent establishment of focal polyneuronal innervation is due not to stability of presynaptic elements maintained past a critical developmental stage but is associated with substantial losses of muscle fibres, leading to a high ratio of nerve fibres to muscle fibres.