Formation and elimination of foreign synapses on adult salamander muscle

Abstract

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. 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. Suppression of foreign synapses was sufficiently thorough that most ceased transmitting entirely. Before reinnervation by the correct nerve 97% of the extensor muscle fibers received functional foreign synapses while 4-6 mo. after correct nerve return only 35% of the fibers retained foreign synapses, with weak transmission. Two lines of evidence indicated that suppressed foreign synapses were lost from the muscle: a 2nd correct nerve lesion 6-8 mo. after the initial denervation produced no significant increase in the proportion of fibers with foreign transmission and 4 muscles which showed complete suppression of foreign transmission were bathed in medium containing horseradish peroxidase (hrp) and the correct nerve was stimulated repetitively. Subsequent histochemical staining for hrp and examination of synapses by EM revealed that 94% of the axon terminals had hrp incorporated in vesicles. Thus at least that percentage of all identifiable synapses were from the correct nerve. This ability to eliminate incorrect synapses in favor of correct ones may be a general characteristic of embryonic nervous systems, which in adulthood was retained by salamanders but lost by most other animals.