Release of synaptic zinc is substantially depressed by conventional brain slice preparations

Research on synaptically-released zinc is frequently done in vitro with acute brain slice preparations. We show here the in vitro hippocampal slice preparation has two major pitfalls for zinc research. First, up to 50% of the synaptic zinc is lost during slice cutting and/or the first 10 min of slice incubation, with the losses being most pronounced on the edges of the slice. Second, the release of the remaining zinc from a slice is substantially depressed (up to 50%) at the low temperatures (32 degrees C) typically used for brain slice studies. In concert, these effects reduce zinc release about 75% in vitro, compared to in vivo. Implications for research on synaptically-released zinc are discussed.