The self-regulating synapse: A functional role for the co-existence of neuroactive substances

Although the co-localizations of neuroactive substances, such as transmitters and peptides, in identified neurons is now a common histochemical phenomenon, the physiological roles and functional significance of such co-existence are largely unknown. Using the vertebrate retina as a model for the central nervous system, we have examined the relationship between co-existence and co-function. We propose here that the co-localization of neuroactive substances in a synaptic terminal provides the structural configuration to ensure the co-release of two or more predetermined substances into the same synaptic cleft, resulting in the capability of the presynaptic neuron to stringently regulate its own activities and output.