The Impact of Synaptic Zn(2+) Dynamics on Cognition and Its Decline

The basal levels of extracellular Zn(2+) are in the range of low nanomolar concentrations and less attention has been paid to Zn(2+), compared to Ca(2+), for synaptic activity. However, extracellular Zn(2+) is necessary for synaptic activity. The basal levels of extracellular zinc are age-dependently increased in the rat hippocampus, implying that the basal levels of extracellular Zn(2+) are also increased age-dependently and that extracellular Zn(2+) dynamics are linked with age-related cognitive function and dysfunction. In the hippocampus, the influx of extracellular Zn(2+) into postsynaptic neurons, which is often linked with Zn(2+) release from neuron terminals, is critical for cognitive activity via long-term potentiation (LTP). In contrast, the excess influx of extracellular Zn(2+) into postsynaptic neurons induces cognitive decline. Interestingly, the excess influx of extracellular Zn(2+) more readily occurs in aged dentate granule cells and intracellular Zn(2+)-buffering, which is assessed with ZnAF-2DA, is weakened in the aged dentate granule cells. Characteristics (easiness) of extracellular Zn(2+) influx seem to be linked with the weakened intracellular Zn(2+)-buffering in the aged dentate gyrus. This paper deals with the impact of synaptic Zn(2+) signaling on cognition and its decline in comparison with synaptic Ca(2+) signaling.