The Impact of Synaptic Zn Dynamics on Cognition and Its Decline.

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