Electrophysiological approaches to the study of neuronal exocytosis and synaptic vesicle dynamics

The cornerstone of synaptic transmission is the calcium-dependent fusion of synaptic vesicles with the plasma membrane and the release of neurotransmitter into the synaptic cleft. Renewed interest in the mechanisms that regulate these important first steps in neuronal communication has been sparked by recent advances in the identification of molecular interactions that underlie these processes and by the development of electrophysiological techniques that permit the direct examination of these processes in realtime. This review will present the emerging view of neuronal exocytosis and endocytosis that has developed as a consequence of these new electrophysiological approaches. Where instructive, results will be discussed in light of other new developments in the field in order to give the reader a comprehensive understanding of our current knowledge. To set the stage, we begin with an overview of the traditional approach to the study of neurotransmitter release, electrical recordings from pairs of synaptically-connected cells and discuss the applicibility of this approach to the study of exocytosis and synaptic vesicle dynamics in the central nervous system. The review win then focus on its main theme, the use of membrane capacitance measurements and whole-terminal patch-clamp recording techniques to directly monitor calcium-dependent synaptic vesicle fusion and retrieval in central neurons. Next, carbon fiber amperometry will be introduced, and information about the mechanics of secretory vesicle fusion and neurotransmitter release obtained with carbon fiber amperometry will be presented. Finally, combinations and refinements of these electrophysiological approaches will be discussed.