Splitting the quantum: regulation of quantal release during vesicle fusion

One of the most enduring central hypotheses in neurobiology has been that neurotransmission is determined by the quantal release of neurotransmitter. An important assumption has been that quantal size (amount of transmitter released per vesicle) is constant. Recent work has established that, for dense-core granules, quantal size can be varied by stimulation frequency, changes in second messenger levels and modification of the proteins of the exocytotic machinery. These data argue against the long-held belief in the universality of the quantal hypothesis, and raise important but controversial questions as to whether the same mechanisms could also regulate release from synaptic vesicles and contribute to synaptic plasticity.