Complexins (Cplxs) are small synaptic proteins that cooperate with 
SNARE-complexes in the control of synaptic vesicle (SV) fusion. Studies 
involving genetic mutation, knock-down, or knock-out indicated two key functions 
of Cplx that are not mutually exclusive but cannot easily be reconciled, one in 
facilitating SV fusion, and one in "clamping" SVs to prevent premature fusion. 
Most studies on the role of Cplxs in mammalian synapse function have relied on 
cultured neurons, heterologous expression systems, or membrane fusion assays in 
vitro, whereas little is known about the function of Cplxs in native synapses. 
We therefore studied consequences of genetic ablation of Cplx1 in the mouse 
calyx of Held synapse, and discovered a developmentally exacerbating phenotype 
of reduced spontaneous and evoked transmission but excessive asynchronous 
release after stimulation, compatible with combined facilitating and clamping 
functions of Cplx1. Because action potential waveforms, Ca(2+) influx, readily 
releasable SV pool size, and quantal size were unaltered, the reduced synaptic 
strength in the absence of Cplx1 is most likely a consequence of a decreased 
release probability, which is caused, in part, by less tight coupling between 
Ca(2+) channels and docked SV. We found further that the excessive asynchronous 
release in Cplx1-deficient calyces triggered aberrant action potentials in their 
target neurons, and slowed-down the recovery of EPSCs after depleting stimuli. 
The augmented asynchronous release had a delayed onset and lasted hundreds of 
milliseconds, indicating that it predominantly represents fusion of newly 
recruited SVs, which remain unstable and prone to premature fusion in the 
absence of Cplx1.