ABSTRACT

Exocytosis of neurotransmitters mediates the rapid communication between neurons at synaptic sites, where the neurotransmitters are released from the nerve endings of a presynaptic neuron and received by the postsynaptic membrane of another cell. Upon nerve stimulation, a transient increase in calcium concentration triggers synaptic vesicles to fuse with the plasma membrane. Synaptic vesicles release their neurotransmitter content in the intersynaptic space, then recycle and reload with newly synthetized neurotransmitter. In the past years the physiology and pharmacology of exocytosis has been extensively studied (Pevnsner and Scheller, 1994; Niemann et al., 1994; Sudhof, 1995). One approach particularly useful in the identification of the functional properties of the neuroexocytosis apparatus has been the use of natural neurotoxins as tools to characterize and/or localize their target molecules at the presynaptic terminal. Several toxins, active at the presynaptic site, are known to affect the structure and/or the function of nerve terminals. These toxins have been classified into three groups (Rosenthal and Meldolesi 1989): the blockers of neurosecretion, e.g. botulinum and tetanus toxins, acting intracellularly by a selective proteolysis of specific proteins of the exocytotic machinery; the presynaptic stimulatory toxins, like the α-latrotoxin, acting at the nerve terminal plasmamembrane; and the quite heterogeneous group of toxins addressed to membrane channels and receptors. This review describes the use of these toxins in morphological studies aimed at characterizing specific properties of the exocytotic apparatus in different neuronal models.