Imaging free zinc in synaptic terminals in live hippocampal slices

Some glutamatergic synapses in the mammalian central nervous system exhibit high levels of free ionic zinc in their synaptic vesicles. The precise role of this vesicular zinc remains obscure: despite suggestive evidence for zinc as a neuromodulator. As a step towards elucidating the role of free zinc in the brain we have developed a method for imaging zinc release in live brain slices. A newly synthesized zinc-sensitive fluorescent probe, N-(6-methoxy-8-quinolyl)-p-carboxybenzo sulphonamide (TFLZn), was used to monitor intracellular zinc in live rat hippocampal slices. The dye loaded into the zinc-rich synaptic vesicles of the messy fibre terminals in the hippecampal formation. Direct electrical stimulation of the messy fibre pathway diminished the fluorescence in the messy fibre terminals, consistent with a stimulus-dependent zinc release. The synaptic release of zinc was followed by the rapid replenishment of the zinc levels in vesicles from an as yet unidentified intracellular zinc source. Furthermore, we present evidence that zinc may play a role in a form of long-term potentiation exhibited by the messy fibre pathway. (C) 1997 IBRO. Published by Elsevier Science Ltd.