ABSTRACT
A simple way to achieve inter-cellular communication involves release of a chemical substance which signals through receptor molecules that exist on the same or neighbouring cells. This principle lies at the heart of the signalling process utilised by the synapse, the basic unit on which an integral nervous system is built (Jessell and Kandel, 1993). At fast chemical synapse the elementary signalling event involves a depolarization dependent Ca2+ influx into the presynaptic terminal that triggers the release of the neurotransmitter to be sensed by the postsynaptic cell (Augustine et al., 1987). In the most rapid forms of chemical transmission this process is complete within a millisecond, indicating that a highly ordered sequence regulates the release and detection of neurotransmitter (Llinas et al., 1992). A key aspect of this ordered process is the morphological specialization of the synapse which ensures that the presynaptic terminal from which transmitter is released lies juxtapposed to the receptor containing postsynaptic membrane (Peters et al., 1991)
Studies of Katz and colleagues, utilising the electrophysiologically accessible neuromuscular junction, provided an early frame work for understanding transmitter release, the process that initiates synaptic transmission (Katz, 1971). They showed that the rapid, Ca2+dependent release events were made up of discrete packets or quanta of transmitter. In parallel, morphological investigations revealed that the presynaptic terminal contained an abundance of small clear intracellular organelles, including a population that appeared associated with the presynaptic plasmamembrane (Palade and Palay, 1954). These functional and structural observations were considered to be related and led to the vesicle hypothesis of release. The latter postulated that release was fuelled by Ca2+ dependent secretion of transmitter from the synaptic vesicles that appeared
docked at the active zone, a morphological specialisation of the presynaptic plasmamembrane. Subsequent studies of nerve terminals frozen while undergoing release provided morphological evidence for the collapse of synaptic vesicles into the plasmamembrane during neurotransmitter release (Heuser et al., 1979). More recent experiments using techniques that directly measure released transmitter (Bruns and Jahn, 1995) or the membrane added to the plasmamembrane (von Gersdorf and Matthews, 1994), from fusing vesicles have largely confirmed the vesicle hypothesis of release.
