Novel Distinctive Roles of Docking Proteins in Short-term Synaptic Plasticity of Frog Neuromuscular Transmission Revealed by Botulinum Neurotoxins

Short-term synaptic plasticity (SSP) is a basic mechanism for temporal processing of neural information in synaptic transmission. Facilitation, the fastest component of SSP, has been extensively investigated with regard to Ca2+ signaling and other relevant substances. However, systematic analyses on the slower components of SSP, originated by Magleby and Zengel, have remained stagnant for decades, as few chemicals directly modifying these slower components have been identified. In combination with refined experimental protocols designed to study the stimulation frequency-dependence of SSP and botulinum neurotoxins A and C (BoNT-A and BoNT-C), we investigated SSP of frog neuromuscular transmission to clarify the roles of synaptosomal-associated protein of 25 kDa (SNAP-25) and syntaxin, SNARE proteins exclusively participating in vesicular events including docking, priming and exocytosis. We found that BoNT-A treatment eliminated slow potentiation, and BoNT-C poisoning abolished intermediate augmentation, two components of SSP. Fast facilitation was maintained after double poisoning with BoNT-A and -C, but the postsynaptic response became biphasic. A novel depression, termed repression, emerged by double poisoning. Repression was different from depletion because it developed even at a low-frequency stimulation of 1 Hz. We conclude that SNAP-25 and syntaxin not only play roles as cooperative exocytotic machinery, but also have roles in SSP.