The Way Traveled from A to Inhibition of LTP

The molecular calcium sensor responsible for transmitter release has been one of the holy grails of molecular neurobiology. For a number of years, attention has focused on synaptotagmins that have many of the necessary attributes. For example, evoked release is reduced when synaptotagmin I is blocked or eliminated. However, the story is not so simple, because loss of synaptotagmins does not completely eliminate calcium-dependent transmitter release. Evoked transmitter release includes both a fast, synchronous component as well as a slower, asynchronous component. In this issue, Nishiki and Augustine investigated the role of synaptotagmins on transmitter release in mouse hippocampal microisland cultures. They compared the kinetics of EPSCs in synaptotagmin I knock-outs with wild-type neurons. Fast release was lost, but slower, sustained release of transmitter increased. As a result, the total amount of released transmitter was the same in synaptotagmin I knock-outs as in wild type. Thus synaptotagmin I synchronizes fast release while simultaneously reducing slow asynchronous release.