Significance of the degree of synaptic Zn²⁺ signaling in cognition

Zinc is a trace nutrient for the brain and a signal factor to serve for brain function. A portion of zinc is released from glutamatergic (zincergic) neuron terminals in the brain. Synaptic Zn(2+) signaling is involved in synaptic plasticity such as long-term potentiaion (LTP), which is a cellular mechanism of memory. The block and/or loss of synaptic Zn(2+) signaling in the hippocampus and amygdala with Zn(2+) chelators affect cognition, while the role of synaptic Zn(2+) signal is poorly understood, because zinc-binding proteins are great in number and multi-functional. Chronic zinc deficiency also affects cognition and cognitive decline induced by zinc deficiency might be associated with the increase in plasma glucocorticoid rather than the decrease in synaptic Zn(2+) signaling. On the other hand, excess glutamatergic (zincergic) neuron activity induces excess influx of extracellular Zn(2+) into hippocampal neurons, followed by cognitive decline. Intracellular Zn(2+) dynamics, which is linked to presynaptic glutamate release, is critical for LTP and cognitive performance. This paper deals with insight into cognition from zinc as a nutrient and signal factor.