Long term changes in augmentation, potentiation, and depression of transmitter release as a function of repeated synaptic activity at the frog neuromuscular junction.

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Abstract
End-plate potentials [EPP] were recorded from frog neuromuscular junctions under conditions of low quantal content to study the long-term effects of repeated synaptic activity on transmitter release. The nerve terminal was presented with 30-100 successive conditioning-testing trials applied once every 7-10 min over a 4-16 h period. Each conditioning-testing trial consisted of a 200-600 impulse conditioning train followed by a series of testing impulses. The magnitudes and time constants of decay of augmentation and potentiation following each successive conditioning train were determined by measuring the EPP amplitudes resulting from the testing impulses. The magnitude of augmentation immediately following the conditioning trains increased an average of 3.4 times (range 1-20) with successive trials. As the magnitude of augmentation increased with successive trials the decay of augmentation deviated from a simple exponential, decaying faster immediately after the conditioning train. This faster decay led to a 20% decrease with successive trials in estimates of the time constant obtained from the first 10 or 20 s of the decay of augmentation. The deviation of the decay of augmentation from a simple exponential could be accounted for if augmentation was related to the 4th power of some substance which decays with a simple exponential time course. Some alternative explanations for the non-exponential decay of augmentation were discussed. The magnitude of potentiation increased or decreased about 25% with successive trials. The time constant characterizing the decay of potentiation increased an average of 1.5 times (range 0.8-5 times) with successive trials. The increase in the magnitude of augmentation with successive trials was accompanied by a similar increase in the magnitude of the EPP amplitudes during the conditioning trains, suggesting that augmentation develops during the conditioning train. In some preparations augmentation appeared to be the major factor acting to increase EPP amplitudes during the conditioning train, having a greater effect than facilitation or potentiation. If a sufficiently large number of successive trials were applied, a depression of EPP amplitudes developed during the conditioning trains, and estimates of the magnitude of potentiation following the depressed conditioning trains were reduced. In contrast to potentiation, the magnitude of augmentation continued to increase for a few successive trials after the onset of depression, even though the amount of depression during the conditioning train was also increasing with successive trials. This observation that the magnitude of augmentation could increase at the same time that the magnitude of depression was increasing suggests that augmentation and depression do not arise from inverse changes in a common process. The differential effects of successive trials on augmentation and potentiation suggest that at least some of the factors involved in increasing transmitter release by these processes are different for the 2 processes.