Characteristic of Extracellular Zn2+ Influx in the Middle-Aged Dentate Gyrus and Its Involvement in Attenuation of LTP.

An increased influx of extracellular Zn2+ into neurons is a cause of cognitive decline. The influx of extracellular Zn2+ into dentate granule cells was compared between young and middle-aged rats because of vulnerability of the dentate gyrus to aging. The influx of extracellular Zn2+ into dentate granule cells was increased in middle-aged rats after injection of AMPA and high K+ into the dentate gyrus, but not in young rats. Simultaneously, high K+-induced attenuation of LTP was observed in middle-aged rats, but not in young rats. The attenuation was rescued by co-injection of CaEDTA, an extracellular Zn2+ chelator. Intracellular Zn2+ in dentate granule cells was also increased in middle-aged slices with high K+, in which the increase in extracellular Zn2+ was the same as young slices with high K+, suggesting that ability of extracellular Zn2+ influx into dentate granule cells is greater in middle-aged rats. Furthermore, extracellular zinc concentration in the hippocampus was increased age-dependently. The present study suggests that the influx of extracellular Zn2+ into dentate granule cells is more readily increased in middle-aged rats and that its increase is a cause of age-related attenuation of LTP in the dentate gyrus.