Zinc toxicity has been postulated to contribute to selective neuronal death after transient global ischemia. We have modeled this injury mechanism in acutely-prepared adult rat hippocampal slices exposed to oxygen-glucose deprivation (Canzoniero L.M.T. et al. SFN abstract vol. 26:763,2000); neuronal death in this model is associated with an increase in intracellular zinc, and is reduced by the application of the extracellular chelator, CaEDTA. We have now extended study of the oxygen-glucose deprivation-induced neuronal death to murine hippocampal slices, monitoring intracellular free zinc concentration with the ratiometric dye, FuraZin-1. The FuraZin-1 signal from both CA1 and CA3 areas showed a modest increase after 20 min of oxygen-glucose deprivation. Addition of 1mM CaEDTA to the bathing medium reduced the fluorescent signal from the CA3 area, but not the CA1 area. Next, we examined the slices from ZnT3 knockout mice, kindly provided by Richard Palmiter, that have little or no vesicular zinc in neuron...