Formation and elimination of foreign synapses on adult salamander muscle.

1. Synapses by flexor nerve were induced on denervated extensor muscle in adult salamander forelimbs. Excitatory potentials evoked by these ;foreign' synapses were at first small but increased to normal amplitude within several weeks, in the absence of correct nerve reinnervation.2. Upon return of the correct nerve the efficacy of foreign synaptic transmission began to decline. The time of initiation of this decline correlated well with the resumption of correct nerve transmission. The suppression of foreign transmission involved a reduction in mean quantal content of transmitter release.3. Suppression of foreign synapses was sufficiently thorough that most ceased transmitting entirely. Before reinnervation by the correct nerve 97% of the extensor muscle fibres received functional foreign synapses while 4-6 months after correct nerve return only 35% of the fibres retained foreign synapses, with weak transmission.4. Two lines of evidence indicate that suppressed foreign synapses are lost from the muscle: (a) a second correct nerve lesion 6-8 months after the initial denervation produced no significant increase in the proportion of fibres with foreign transmission and (b) four muscles which showed complete suppression of foreign transmission were bathed in medium containing horseradish peroxidase (h.r.p.) and the correct nerve was stimulated repetitively. Subsequent histochemical staining for h.r.p. and examination of synapses by electron microscopy revealed that 94% of the axon terminals had h.r.p. incorporated in vesicles. Thus at least that percentage of all identifiable synapses were from the correct nerve.5. This ability to eliminate incorrect synapses in favour of correct ones is speculated to be a general characteristic of embryonic nervous systems, which in adulthood is retained by salamanders but lost by most other animals.