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 wide variety of physiological and pathological conditions, and it is important to understand the processes that control their secretion. We have developed a technique that measures neuropeptide secretion with high temporal resolution. This method involves placing an electrophysiological "tag" in a neuropeptide prohormone. The tagged prohormone is subsequently expressed together with an ionotropic receptor that binds the tag. Because the neuropeptide of interest and the tag enter the same population of dense core granules, neuropeptide secretion gives rise to fast, synaptic-like currents. Using this method, we show that peptide secretion can be modulated on a millisecond time scale. This technique could be readily adapted to measure the secretion of any neuropeptide.