Importance of zinc in the central nervous system: The zinc-containing neuron

Zinc is essential to the structure and function of myriad proteins, includi ng regulatory, structural and enzymatic, It is estimated that up to 1 % of the human genome codes for zinc finger proteins. In the central nervous sys tem, zinc has an additional role as a neurosecretory product or cofactor. I n this role, zinc is highly concentrated in the synaptic vesicles of a spec ific contingent of neurons, called "zinc-containing" neurons. Zinc-containi ng neurons are a subset of glutamatergic neurons. The zinc in the vesicles probably exceeds 1 mmol/L in concentration and is only weakly coordinated w ith any endogenous ligand. Zinc-containing neurons are found almost exclusi vely in the forebrain, where in mammals they have evolved into a complex an d elaborate associational network that interconnects most of the cerebral c ortices and limbic structures. Indeed, one of the intriguing aspects of the se neurons is that they compose somewhat of a chemospecific "private line" of the mammalian cerebral cortex, The present review outlines (I) the metho ds used to discover, define and describe zinc-containing neurons; (2) the n euroarchitecture and synaptology of zinc-containing neural circuits; (3) th e physiology of regulated vesicular zinc release; (4) the "life cycle" and molecular biology of vesicular zinc; (5) the importance of synaptically rel eased zinc in the normal and pathological processes of the cerebral cortex; and (6) the role of specific and nonspecific stressors in the release of z inc.