Quantal release of serotonin from presynaptic nerve terminals

Although much is known about the synthesis, storage, break-down and biological importance of serotonin (5-HT) there is little information about its release from presynaptic nerve terminals. For example, in the mammalian CNS it is not known whether 5-HT is released in multimolecular packets (quanta) or whether facilitation of release occurs with successive impulses mobilizing larger numbers of quanta. Other problems concern vesicle recycling after stimulation and the role of calcium entry into presynaptic terminals. Preparations in which such basic questions can be explored directly are provided by individual identified serotonergic neurones isolated from the CNS of a simple invertebrate, the leech. It will be shown that these cells maintain their membrane properties, and continue to synthesize, store and secrete 5-HT in tissue culture. Moreover they make highly specific synaptic connections with certain identified target cells. By a combination of voltage clamp, biochemical and electronmicroscopic techniques it has been shown that serotonin is released in multimolecular packets. The quantal unit size is approx. 15 ?V. Vesicles can be observed to fuse with the presynaptic membrane. With prolonged stimulation vesicle recycling occurs and markers are taken up from extracellular space. Moreover, with trains of impulses, 5-HT release shows clear facilitation, which, as at the neuromuscular junction of the frog, can be explained by the residual calcium hypothesis.