Presynaptic quantal plasticity: Katz's original hypothesis revisited

Changes in the amplitudes of signals conveyed at synaptic contacts between neurons underlie many brain functions and pathologies. Here we review the possible determinants of the amplitude and plasticity of the elementary postsynaptic signal, the miniature. In the absence of a definite understanding of the molecular mechanism releasing transmitters, we investigated a possible alternative interpretation. Classically, both the quantal theory and the vesicle theory predict that the amount of transmitter producing a miniature is determined presynaptically prior to release and that rapid changes in miniature amplitude reflect essentially postsynaptic alterations. However, recent data indicates that short-term and long-lasting changes in miniature amplitude are in large part due to changes in the amount of transmitter in individual released packets that show no evidence of preformation. Current representations of transmitter release derive from basic properties of neuromuscular transmission and endocrine secretion. Reexamination of overlooked properties of these two systems indicate that the amplitude of miniatures may depend as much, if not more, on the Ca(2+) signals in the presynaptic terminal than on the number of postsynaptic receptors available or on vesicle's contents. Rapid recycling of transmitter and its possible adsorption at plasma and vesicle lumenal membrane surfaces suggest that exocytosis may reflect membrane traffic rather than actual transmitter release. This led us to reconsider the disregarded hypothesis introduced by Fatt and Katz (1952; J Physiol 117:109-128) that the excitability of the release site may account for the "quantal effect" in fast synaptic transmission. In this case, changes in excitability of release sites would contribute to the presynaptic quantal plasticity that is often recorded.