Targeting of peptidergic vesicles in cotransmitting terminals

In the present study, we examined the targeting of neuropeptide-containing vesicles in terminals of neurons that release both neuropeptides and classi cal transmitters. Single neurons were electrically stimulated with patterns of activity that were recorded in freely behaving animals. The amount of p eptide release was measured biochemically using a radioimmunoassay, and the targeting of peptidergic vesicles was quantified using immunoelectronmicro scopy. Repeated electrical stimulation of single neurons produced a very la rge increase in peptide release. Peptide release is paralleled by a twofold increase in the number of peptidergic vesicles docked at the portion of th e terminal membrane that is away from the target muscle. This is in stark c ontrast to cholinergic vesicles, which aggregate at, and are released from the conventional release sites in close apposition to the muscle. This diff erential targeting of cholinergic and peptidergic vesicles may play a signi ficant role in the distinct release requirements and spatial and temporal c haracteristics of the actions of conventional and peptidergic transmitters.