Title: Vesicle Pools and Ca2+ Microdomains: New Tools for Understanding Their Roles in Neurotransmitter Release
Abstract: When Tom Jessell and Eric Kandel (1993) reviewed the field of synaptic transmission 5 years ago they concluded that “… our molecular understanding of the physiology of transmitter release has not advanced dramatically since Katz.” This statement in their article in the joint issue of Cell and Neuron, “Signaling at the Synapse,” intended to contrast our grasp of presynaptic physiology with our understanding of postsynaptic events, which had undergone a quantum leap in the preceding decade. They further argued that when considering presynaptic events “… we are entering a more complex arena of organelle cell biology, where function depends less on the properties of single molecules and more on the coordination of a series of molecular events: the targeting of vesicles to and the docking of vesicles at release sites and the assembly of the molecular machinery for fusion and exocytosis.” This statement again has to be seen in contrast to the postsynaptic side, where transmitter action can be understood fairly well by studying the response of a single class of molecules and where the techniques had been available to do so both on a macroscopic and the single molecule level. Turning back to the presynaptic side, it has to be realized that conditions are quite unfavorable indeed. Not only are the majority of presynaptic terminals quite small and inaccessible to electrodes and other probes, but techniques to monitor the release process on the level of a single cell, a single terminal, or even a single vesicle were hardly available, except for observing the postsynaptic effect of the release process. This, however, is an indirect approach, the merits and pitfalls of which have become apparent in lengthy disputes about the presynaptic versus postsynaptic origin of plastic changes.