A novel technique that measures peptide secretion on a millisecond timescale reveals rapid changes in release

Neuropeptides are ubiquitous transmitters that have been implicated in a wi de variety of physiological and pathological conditions, and it is importan t to understand the processes that control their secretion. We have develop ed a technique that measures neuropeptide secretion with high temporal reso lution. This method involves placing an electrophysiological "tag" in a neu ropeptide prohormone. The tagged prohormone is subsequently expressed toget her with an ionotropic receptor that binds the tag. Because the neuropeptid e of interest and the tag enter the same population of dense core granules, neuropeptide secretion gives rise to fast, synaptic-like currents. Using t his method, we show that peptide secretion can be modulated on a millisecon d time scale. This technique could be readily adapted to measure the secret ion of any neuropeptide.