Merits and Limitations of Vesicle Pool Models in View of Heterogeneous Populations of Synaptic Vesicles

The concept of a readily releasable pool (RRP) of synaptic vesicles has been used extensively for the analysis of neurotransmitter release. Traditionally the properties of vesicles in such a pool have been assumed to be homogeneous, and techniques have been developed to determine pool parameters, such as the size of the pool and the probability with which a vesicle is released during an action potential. Increasing evidence, however, indicates that vesicles may be quite heterogeneous with respect to their release probability. The question, therefore, arises: what do the estimates of pool parameters mean in view of such heterogeneity? Here, four methods for obtaining pool estimates are reviewed, together with their underlying assumptions. The consequences of violation of these assumptions are discussed, and how apparent pool sizes are influenced by stimulation strength is explored by simulations.