| dc.description.abstracteng | Complexins are small synaptic proteins which cooperate with the SNARE-complex in synaptic transmission. Different roles of complexins in the regulation of vesicle exocytosis have been proposed. Based on the results of genetic mutation or knock-down or knock-out studies, it is generally agreed that complexins are involved in vesicle priming and exocytosis for fast synchronous release and in clamping vesicles to prevent asynchronous release. However, depending on cell type, organism and experimental approach used, complexins appear to either facilitate or inhibit vesicle fusion.
Here, we study the function of complexin I at the mouse calyx of Held synapse. By taking advantage of the large size of the calyx terminal, allowing direct patch-clamp recordings, we investigate the consequences of the loss of function of complexin I. We demonstrate a developmentally aggravating phenotype of reduced EPSC amplitudes and enhanced asynchronous release. Because action potential waveform, Ca2+ influx, readily releasable pool, and quantal size were all unaltered, we concluded that the reduced synaptic strength in complexin I-deficient synapses was caused by decreased vesicle release probability by either a changed Ca2+ sensitivity of the release machinery and/or a changed coupling between Ca2+ channels and docked vesicles. The strongly enhanced asynchronous release in complexin I-deficient calyx synapses triggered aberrant action potentials in MNTB principal neurons, and slowed-down the recovery of action potential-evoked EPSCs after depleting stimulus trains. Restricting asynchronous release augmented subsequent synchronous release, suggesting that synchronous and asynchronous release competed for a common pool of vesicles. | de |