HOW CAN EXOCYTOSIS ACCOUNT FOR THE ACTUAL PROPERTIES OF MINIATURE SYNAPTIC SIGNALS

It is broadly accepted that a postsynaptic ''miniature'' is the most e lementary chemically transmitted signal and results from the all-or-no ne release of transmitter packaged in a single presynaptic vesicle. Hi therto, it has not been possible to directly verify this renowned repr esentation, although it is consistent with evidence of vesicle traffic and, following an intense period of release, vesicle depletion. Howev er, vesicle traffic involving molecular components similar to those im plicated in transmitter release has been attributed to other functions including membrane repair. Furthermore, as a number of investigators have recently proposed, miniature signals recorded at peripheral and c entral synapses may actually reflect several rather than a single disc harge of transmitter. It is not clear whether such putative multiple-d ischarge miniatures represent near-synchronous exocytoses of several v esicles or a burst of openings in a pore that couples a vesicle with t he outer membrane. In any case, despite the popularity of the vesicula r hypothesis, the molecular mechanism involved in synchronizing fast e lementary secretion has not yet been elucidated. Interdependencies amo ng subminiature discharges composing a miniature have suggested that t he underlying process is a regenerative signal restricted to a presyna ptic terminal unit, confirming Fatt and Katz's first speculation on mi niatures, which was not vesicular exocytosis [Fatt and Katz (1952), J. Physiol., 117:109-128]. Here we discuss the possibility that this reg enerative signal might be a localized cytosolic Ca2+ transient and att empt to reconcile this hypothesis with the exocytotic models proposed to explain fast transmitter release. (C) 1995 Wiley-Liss, Inc.