Unique response of zinc in the hippocampus to behavioral stress and attenuation of subsequent mossy fiber long-term potentiation

Extracellular zinc in the hippocampus is decreased by novelty stress. The significance of zinc movement in acute stress is unknown. In the present study, response of extracellular zinc in the hippocampus was examined after exposure to tail suspension, a behavioral stress. In rats subjected to hippocampal perfusion, thirty-second tail suspension elicited a short increase in extracellular glutamate and a persistent decrease in extracellular zinc, which continued for 60 min. These results suggest that zinc influx into hippocampal cells is facilitated by acute behavioral stress. Furthermore, the influence of the facilitated zinc influx in mossy fiber long-term potentiation (LTP) was evaluated in hippocampal slices prepared from rats 1 h after tail suspension. Mossy fiber LTP was significantly attenuated. Perfusion with 100 μM ZnCl2 prior to LTP induction was performed to facilitate zinc influx. The zinc perfusion also attenuated mossy fiber LTP. On the other hand, perfusion with 50 μM glutamate did not attenuate it. The attenuation of mossy fiber LTP by tail suspension was completely restored when rats were pretreated with clioquinol (30 mg/kg) to block the action of chelatable zinc. The present study indicates that exposure to tail suspension attenuates subsequent mossy fiber LTP. It is likely that the facilitated zinc influx by tail suspension, which seems to be linked to glutamate signaling, is involved in attenuation of subsequent mossy fiber LTP.