Overexpression of synaptotagmin modulates short-term synaptic plasticity at developing neuromuscular junctions.

The level of synaptotagmin I or II in developing spinal neurons was increased by injection of synaptotagmin messenger RNA into early blastomeres of Xenopus embryos. The effect of overexpression of synaptotagmin on synaptic function was assayed in Xenopus nerve-muscle cultures within two days after injection. At neuromuscular synapses made by synaptotagmin-overexpressing neurons, the frequency of miniature postsynaptic currents was markedly reduced, while their mean amplitude was unchanged, as compared to those of control neurons in the same culture. The amplitude of evoked postsynaptic currents elicited by low-frequency test stimuli was not affected by overexpression. However, synapses made by synaptotagmin-overexpressing neurons exhibited significantly higher paired-pulse facilitation and reduced tetanus-induced depression of the synaptic response, and there was also an increased number of synaptic vesicles at regions 100-300 nm from the plasmalemma at such synapses. These results show that synaptotagmins can exert an inhibitory action on the spontaneous exocytosis of synaptic vesicles. The effects on short-term plasticity suggest that synaptotagmin may facilitate vesicular supply for the evoked release during higher frequency transmission.