FIRST STEP NEGATIVE FEEDBACK ACCOUNTS FOR INHIBITION OF FAST NEUROTRANSMITTER RELEASE

This paper is concerned with feedback inhibition of neurotransmitter r elease by the neurotransmitter itself. We put forward the idea that, s imilar to multistep biochemical processes, feedback inhibition acts on the initial step in the chain of events that lead to release. Using e xperimental results carried out on glutamatergic synapses in crayfish, we show that the ''first step'' hypothesis can account for all experi mental results. Our modeling suggests that the biochemical implementat ion of this inhibition involves the formation of a second messenger, w hose production is triggered by binding of transmitter to the autorece ptor. We argue that the autoreceptor is a key part of the release-indu cing machinery. (C) 1997 Academic Press Limited.