Do they or don't they?

Abstract

It is felt that the objectives of this conference were met and a great of new information was presented on the characterization of presynaptic receptors and their mechanisms of action and pathophysiological roles. There is still a difference of opinion concerning the precise physiological role of presynaptic autoreceptors. It is possible that autoregulation may not exist at all junctions or synapses. It is also not clear if autoregula- tion takes place at each varicosity, upstream of terminal varicosities, or by lateral regulation (one varicosity to another). Possible physiological functions of autoregula- tion may include: pulse-to-pulse regulation of transmitter release during nerve stimulation; upstream or lateral regulation of release from various varicosities; modulation of release during periods of rest or during periods in which the frequency of nerve stimulation is low; and modulation of release during periods of very intense stimulation. Finally, autoregulation may serve as a physiological antagonist to facilitation of transmitter release that is known to take place in some neurons during nerve stimulation. The conference provided a clearer understanding of the objections to attributing a physiological role to autoregulation and an understanding of what information is lacking. Challenges for future research will be to unravel the precise physiological and pathophysiological roles of presynaptic receptor- modulation of neurotransmission, to explain better why some results are inconsistent with the autoregulation hypothesis, and to define further the mechanisms by which activation of autoreceptors and heteroreceptors are linked to inhibition or facilitation of transmitter release.