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Significance Neuropeptides, which affect mood and behavior, are synthesized in the soma and delivered to nerve terminals for storage and release. Yet, among identified neurons, there is great variation in the abundance of neuropeptides in terminals. Demonstrated transcriptional regulation of neuropeptide synthesis supports the view that presynaptic neuropeptide stores are proportional to synthesis-driven delivery of neuropeptide-containing vesicles to terminals. However, we show that nerve terminals with dramatically different neuropeptide stores are supported by identical vesicle delivery and differ instead in efficiency of vesicle capture. Vesicle capture in the terminal is under transcriptional control and influences vesicle distribution and replacement as well as neuropeptide accumulation for release. Thus, vesicle capture is a major determinant of nerve terminal function.

Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals