The SNARE-binding Protein Complexin Modulates the Kinetics of Neurotransmitter Release and Short-term Synaptic Plasticity

Abstract

Neurotransmitter release requires calcium-dependent synaptic vesicle fusion mediated by Synaptotagmin 1 and the SNARE complex. Complexin is a synaptic binding partner of the neuronal SNARE complex and has been implicated as an effector of vesicle priming and fusion, and as a synaptic vesicle fusion clamp. However, the precise physiological role of complexin in vesicle fusion and short-term synaptic plasticity is unknown. Here, we investigate the role of complexin in neurotransmitter release and short-term synaptic plasticity at the Drosophila neuromuscular junction (NMJ). We present a thorough analysis of synaptic transmission in complexin null mutants and complexin overexpression strains using voltage-clamp recordings at the NMJ. Kinetic analysis of evoked current reveals that synchronous and asynchronous release depends critically on the level of complexin expression. Additionally, complexin regulates early short-term synaptic depression and facilitation in opposite fashion, through modulation of release probability and the immediately releasable pool. We propose that complexin decreases the free energy of SNARE complex-mediated priming and generates an energetic barrier at a late stage by clamping vesicles in the immediately releasable pool.