Depression of developing neuromuscular synapses induced by repetitive postsynaptic depolarizations

Effect of postsynaptic activity on the synaptic efficacy was studied in Xenopus nerve-muscle cultures. Repetitive post-synaptic depolarizations induced by injection of current pulses into singly innervated myocytes resulted in significant reduction in the frequency of spontaneous synaptic currents and the amplitude of nerve-evoked synaptic currents at the majority of synapses that showed immature synaptic properties. Repetitive hyperpolarizations and steady depolarizations of similar duration were without effect. The depolarization-induced synaptic depression appeared to result predominately from a reduced ACh secretion from the presynaptic nerve terminal. Buffering the myocyte cytosolic Ca²⁺ at a low level with intracellular loading of a Ca²⁺ buffer, 1,2-bis(2-aminophenoxy)ethane- N,N,N,N-tetra-acetic acid (BAPTA), significantly reduced the effect of the depolarizations. Thus postsynaptic electrical activity can regulate the synaptic efficacy of the developing neuromuscular synapses and the regulation may be mediated by retrograde transsynaptic interactions.