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*
NeuroBio Tex, Inc., Galveston, TX 77550,
MicroFab Technologies, Inc., Plano, TX 75075,
**
Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77550 and
University of Maryland, Baltimore, MD 21201
2To whom correspondence should be addressed.
Zinc is essential to the structure and function of myriad proteins, including regulatory, structural and enzymatic. It is estimated that up to 1% of the human genome codes for zinc finger proteins. In the central nervous system, zinc has an additional role as a neurosecretory product or cofactor. In this role, zinc is highly concentrated in the synaptic vesicles of a specific contingent of neurons, called "zinc-containing" neurons. Zinc-containing neurons are a subset of glutamatergic neurons. The zinc in the vesicles probably exceeds 1 mmol/L in concentration and is only weakly coordinated with any endogenous ligand. Zinc-containing neurons are found almost exclusively in the forebrain, where in mammals they have evolved into a complex and elaborate associational network that interconnects most of the cerebral cortices and limbic structures. Indeed, one of the intriguing aspects of these neurons is that they compose somewhat of a chemospecific "private line" of the mammalian cerebral cortex. The present review outlines (1) the methods used to discover, define and describe zinc-containing neurons; (2) the neuroarchitecture and synaptology of zinc-containing neural circuits; (3) the physiology of regulated vesicular zinc release; (4) the "life cycle" and molecular biology of vesicular zinc; (5) the importance of synaptically released zinc in the normal and pathological processes of the cerebral cortex; and (6) the role of specific and nonspecific stressors in the release of zinc.
KEY WORDS: • zinc-containing neurons • glutamate • metallothionein • excitotoxicity GABA • Alzheimer’s disease
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