Differential Autoregulation of Serotonin Secretion at Different Structures of Serotonergic Neurons

Serotonin (5-HT) performs a wide range of neuromodulatory actions in the nervous system, including the regulation of the neurons that release it, by activation of several types of autoreceptors that modulate their electrical activity, as well as its own release. 5-HT neurons release serotonin in different manners from different subcellular structures, including the presynaptic terminals, the somatodendritic region and the axons. The different releasing structures of the same neurons have different types of autoreceptors, which exert differential auto-regulatory effects. Here we critically review the evidence of serotonergic autoregulation, both in mammals and in invertebrates, with particular emphasis on studies of serotonergic Retzius neurons of the leech, which have been a model for detailed studies of serotonin secretion from different neuronal structures. In these neurons serotonin produces different and even opposite effects on different releasing structures, such as the presynaptic terminals and the soma, through activation of different types of autoreceptors, thus increasing the specialization of the mechanisms that regulate exocytosis from each site. The differential autoregulation of serotonin release from different structures enables a single neuron to exert a variety of different functions in the nervous system.