Zinc-containing neurons are cells that sequester zinc in their presynaptic vesicles and release it in a calcium- and impulse-dependent manner. The zinc-containing neurons are a subclass of the glutaminergic neurons: all known zinc-containing pathways are also glutaminergic pathways. With a few exceptions, zinc-containing neurons are located only in the telencephalon. The major glutaminergic systems of the brain stem, thalamus, and cerebellum, for example, all lack vesicular zinc, whereas many cerebrocortical systems are zinc containing. Within the telencephalon, the zinc-containing fiber systems form a vast associational network that reciprocally interconnects isocortical, allocortical and ''limbic'' structures. Because the hippocampal, amygdalar, and perirhinal regions are prominent nodes in this network, it is presumed that vesicular zinc is involved in epileptic phenomena (in pathology) and (in normal function) in the synaptic plasticity of developmental and experiential learning. Zinc ions are potent modulators of amino acid receptors [especially the N-methyl-D-aspartate (NMDA) receptor] and corelease of zinc along with glutamate would provide a mechanism for modulating postsynaptic excitability levels. One useful hypothesis is that synaptically released zinc controls a ''window'' of postsynaptic excitability, having little or no effect at physiological firing rates, but selectively depressing excitability (by NMDA receptor depression) when firing rates reach dangerous, paroxysmal levels.

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