Desynchronization of Multivesicular Release Enhances Purkinje Cell Output

The release of neurotransmitter-filled vesicles after action potentials occurs with discrete time courses: submillisecond phasic release that can be desynchronized by activity followed by "delayed release" that persists for tens of milliseconds. Delayed release has a well-established role in synaptic integration, but it is not clear whether desynchronization of phasic release has physiological consequences. At the climbing fiber to Purkinje cell synapse, the synchronous fusion of multiple vesicles is critical for generating complex spikes. Here we show that stimulation at physiological frequencies drives the temporal dispersion of vesicles undergoing multivesicular release, resulting in a slowing of the EPSC on the millisecond timescale. Remarkably, these changes in EPSC kinetics robustly alter the Purkinje cell complex spike in a manner that promotes axonal propagation of individual spikelets. Thus, desynchronization of multivesicular release enhances the precise and efficient information transfer by complex spikes.